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638 records returned

Antiplasmodial activity of quinones: roles of aziridinyl substituents and the inhibition of Plasmodium falciparum glutathione reductase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although quinones have been the subject of great interest as possible antimalarial agents, the mechanism of their antimalarial activity is poorly understood. Flavoenzyme electrontransferase-catalyzed redox cycling of quinones, and their inhibition of the antioxidant flavoenzyme glutathione reductase (GR, EC 1.8.1.7) have been proposed as possible mechanisms. Here, we have examined the activity of a number of quinones, including the novel antitumour agent RH1, against the malaria parasite Plasmodium falciparum strain FcB1 in vitro, their single-electron reduction rates by P. falciparum ferredoxin:NADP(+) reductase (PfFN...
Source: Archives of Biochemistry and Biophysics - November 14, 2009 Category: Biochemistry Authors: Grellier P, Marozienė A, Nivinskas H, Sarlauskas J, Aliverti A, Cėnas N Tags: Arch Biochem Biophys Source Type: journals

LC-MS/MS analysis of epoxyalcohols and epoxides of arachidonic acid and their oxygenation by recombinant CYP4F8 and CYP4F22.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CYP4F22 and CYP4F8 are expressed in epidermis, and mutations of CYP4F22 are associated with lamellar ichthyosis. Epoxyalcohols (HEETs) and epoxides (EETs) of 20:4n-6 appear to be important for the water permeability barrier of skin. Our aim was to study the MS/MS spectra and fragmentation of these compounds and to determine whether they were oxidized by CYP4F22 or CYP4F8 expressed in yeast. HEETs were prepared from 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 12-HPETE, and their [(2)H(8)]labeled isotopomers, and separated by normal phase-HPLC with MS/MS analysis. CYP4F22 oxygenated 20:4n-6 at C-18, whereas metabolit...
Source: Archives of Biochemistry and Biophysics - November 14, 2009 Category: Biochemistry Authors: Nilsson T, Ivanov IV, Oliw EH Tags: Arch Biochem Biophys Source Type: journals

Exploring the dihydrodipicolinate synthase tetramer: how resilient is the dimer-dimer interface?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) is a tetrameric enzyme that catalyses the first committed step of the lysine biosynthetic pathway. Dimeric variants of DHDPS have impaired catalytic activity due to aberrant protein motions within the dimer unit. Thus, it is thought that the tetrameric structure functions to restrict these motions and optimise enzyme dynamics for catalysis. Despite the importance of dimer-dimer association, the interface between subunits of each dimer is small, accounting for only 4.3% of the total monomer surface area, and the structure of the interface is not conserved across specie...
Source: Archives of Biochemistry and Biophysics - November 14, 2009 Category: Biochemistry Authors: Griffin MD, Dobson RC, Gerrard JA, Perugini MA Tags: Arch Biochem Biophys Source Type: journals

Mutation of the hydrophobic motif in a phosphorylation-deficient mutant renders Protein Kinase C delta more apoptotically active.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that this mutation renders PKCdelta apoptotically more active. Furthermore, we found that the mutant PKCdelta-S662A is tyrosine-phosphorylated and translocated to the membrane faster than its wild type counterpart. PMID: 19914197 [PubMed - as supplied by publisher] (Source: Archives of Biochemistry and Biophysics)
Source: Archives of Biochemistry and Biophysics - November 12, 2009 Category: Biochemistry Authors: Karmacharya MB, Jang JI, Lee YJ, Lee YS, Soh JW Tags: Arch Biochem Biophys Source Type: journals

Tyr74 is essential for the formation, stability and function of Plasmodium falciparum triosephosphate isomerase dimer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Plasmodium falciparum triosephosphate isomerase (PfTIM) is known to be functional only as a homodimer. Although many studies have shown that the interface Cys13 plays a major role in the stability of the dimer, a few reports have demonstrated that structurally conserved Tyr74 may be essential for the stability of PfTIM dimer. To understand the role of Tyr74, we have performed molecular dynamics (MD) simulations of monomeric and dimeric PfTIM mutated to glycine and cysteine at position 74. Simulations of the monomer revealed that mutant Tyr74Gly does not produce changes in folding and stability of the monomer. Interesti...
Source: Archives of Biochemistry and Biophysics - November 12, 2009 Category: Biochemistry Authors: Espinoza-Fonseca LM, Wong-Ramírez C, Trujillo-Ferrara JG Tags: Arch Biochem Biophys Source Type: journals

Cloning, sequence analysis and crystal structure determination of a miraculin-like protein from Murraya koenigii.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Earlier, the purification of a 21.4 kDa protein with trypsin inhibitory activity from seeds of Murraya koenigii has been reported. The present study, based on the amino acid sequence deduced from both cDNA and genomic DNA, establishes it to be a miraculin-like protein and provides crystal structure at 2.9 A resolution. The mature protein consists of 190 amino acid residues with seven cysteines arranged in three disulfide bridges. The amino acid sequence showed maximum homology and formed a distinct cluster with miraculin-like proteins, a soybean Kunitz super family member, in phylogenetic analyses. The major difference...
Source: Archives of Biochemistry and Biophysics - November 12, 2009 Category: Biochemistry Authors: Gahloth D, Selvakumar P, Shee C, Kumar P, Sharma AK Tags: Arch Biochem Biophys Source Type: journals

Enhancement of sphingosine kinase 1 catalytic activity by deletion of 21 amino acids from the cooh-terminus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sphingosine kinase 1 (SphK1) responds to a variety of growth factor signals by increasing catalytic activity as it translocates to the plasma membrane (PM). Several studies have identified amino acids residues involved in translocation yet how SphK1 increases its catalytic activity remains to be elucidated. Herein, we report that deletion of 21 amino acids from the COOH terminus of SphK1 (1-363) results in increased catalytic activity relative to wild-type SphK1 (1-384) which is independent of the phosphorylation state of Serine 225 and PMA stimulation. Importantly, HEK293 cells stably expressing the 1-363 protein exhi...
Source: Archives of Biochemistry and Biophysics - November 12, 2009 Category: Biochemistry Authors: Hengst JA, Guilford JM, Conroy EJ, Wang X, Yun JK Tags: Arch Biochem Biophys Source Type: journals

Application of (19)F magnetic resonance to study the efficacy of fluorine labeled drugs in the three dimensional cultured breast cancer cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cellular monitoring of tumor response to treatments is important for drug discovery and drug development in cancer therapy. We studied efficacy of Herceptin, a common breast cancer drug conjugated with a fluorine organic compound, perfluoro-15-crown-5-ether (PFCE) which easily forms biocompatible emulsions. Three new pharmaceutical forms of Herceptin, Herceptin/PFCE, Herceptin/PFCE/Lipoplex and Herceptin/PFCE/HydraLink were synthesized for the ex vivo study of their efficacy in breast cancer treatment. The emulsions were administered to 10(9) cells.mL(-1) of HER-2 positive human adenocarcinoma (MCF-7) cells and the...
Source: Archives of Biochemistry and Biophysics - November 6, 2009 Category: Biochemistry Authors: Bartusik D, Tomanek B Tags: Arch Biochem Biophys Source Type: journals

ATP modulates transcription factors through P2Y(2) and P2Y(4) receptors via PKC/MAPKs and PKC/Src pathways in MCF-7 cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the present work we studied the involvement of PKC and Src in the phosphorylation of ERK1/2, p38 and JNK1 MAPKs and in the modulation of ATF-1, c-Fos, c-Jun and JunD transcription factors by ATP in MCF-7 breast cancer cells. RT-PCR studies and nucleotide sequence analysis confirmed first the expression of P2Y(2) and P2Y(4) receptor subtypes. The use of specific inhibitors and Src antisense oligonucleotides showed that PKC, but not Src, plays a role in the phosphorylation of MAPKs by ATP. ATP stimulated the expression of c-Fos and the phosphorylation c-Jun, Jun D and ATF-1. PKC and Src only participated in c-Fos indu...
Source: Archives of Biochemistry and Biophysics - November 6, 2009 Category: Biochemistry Authors: Bilbao PS, Boland R, Santillán G Tags: Arch Biochem Biophys Source Type: journals

Cholesterol as a factor regulating intracellular localization of annexin A6 in Niemann-Pick type C human skin fibroblasts.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lysosome-like storage organelles (LSOs) play a crucial role in excessive accumulation of cholesterol in the Niemann-Pick type C (NPC) disease characterized by altered vesicular traffic of lipids. Annexin A6 (AnxA6) is mainly present in cytosol but upon elevation of [Ca(2+)](in) binds to membranes. In addition, a pH or cholesterol-dependent mechanism of AnxA6 interaction with membranes was described. We found a several fold enrichment of AnxA6 in LSO compartment in fibroblasts isolated from NPC patients in comparison with fibroblasts from healthy individuals. We observed that AnxA6 relocates from cytosol to LSOs in a ch...
Source: Archives of Biochemistry and Biophysics - November 6, 2009 Category: Biochemistry Authors: Sztolsztener ME, Strzelecka-Kiliszek A, Pikula S, Tylki-Szymanska A, Bandorowicz-Pikula J Tags: Arch Biochem Biophys Source Type: journals

Potential-dependent membrane permeabilization and mitochondrial aggregation caused by anticancer polyarginine-KLA peptides.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The anticancer activity of the polycationic peptide (KLAKLAK)(2), as a possible mitochondria-damaging agent, named KLA (L-form) or kla (D-form), has been increased by the fusion with hepta-arginine cell delivery vectors r7 and R7 (peptides r7-kla and R7-KLA, respectively), as shown in the literature. We demonstrated that 3.6 muM r7-kla or R7-KLA, but not kla, caused significant permeabilization of the inner and the outer membranes of energized rat liver mitochondria. In addition, r7-kla or R7-KLA induced mitochondrial aggregation, thus causing the inhibition of metabolic activity. Potential-dependent mechanism of perme...
Source: Archives of Biochemistry and Biophysics - November 6, 2009 Category: Biochemistry Authors: Lemeshko VV Tags: Arch Biochem Biophys Source Type: journals

Intrinsic hTRF1fluorescence quenching reveals details of telomere DNA binding activity: Impact of DNA length, structure and position of telomeric repeats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report we provide a kinetic assessment of hTRF1 DNA binding activity. Using intrinsic fluorescence quenching we present evidence that hTRF1 binds to both telomeric and non-telomeric DNA with kinetic discrimination to allow stable binding to telomeric tracts of DNA. The position of telomere repeats does not impact binding though the number of repeats and structure does impact binding. Kinetic analysis of DNA-dependent intrinsic tryptophan fluorescence quenching of hTRF1 revealed a two step binding process that is impacted by telomere repeat length, position, and structure. These data are consistent with existing str...
Source: Archives of Biochemistry and Biophysics - October 31, 2009 Category: Biochemistry Authors: Tahmaseb K, Turchi JJ Tags: Arch Biochem Biophys Source Type: journals

Spectroscopic studies of the oxidation of ferric CYP153A6 by peracids: Insights into P450 higher oxidation states.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Our previous rapid-scanning stopped-flow studies of the reaction of substrate-free cytochrome P450cam with peracids [T. Spolitak, J.H. Dawson, D.P. Ballou (2005) J. Biol. Chem. 280, 20300-20309; (2006) J. Inorg. Biochem. 100, 2034-2044; (2008) J. Biol. Inorg.Chem. 13, 599-611] spectrally characterized compound I (ferryl iron plus a porphyrin pi-cation radical (Fe(IV)=O/Por (*+))), Cpd ES, and Cpd II (Fe(IV)=O/Tyr(*) or Fe(IV)=O). We now report that reactions of CYP153A6 with peracids yield all these intermediates, with kinetic profiles allowing better resolution of all forms at pH 8.0 compared to similar reactions with...
Source: Archives of Biochemistry and Biophysics - October 29, 2009 Category: Biochemistry Authors: Spolitak T, Funhoff EG, Ballou DP Tags: Arch Biochem Biophys Source Type: journals

Partial Characterization of the Molecular Nature of Collagen-Linked Fluorescence: Role of Diabetes and End-Stage Renal Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Collagen-linked fluorescence at excitation/emission 370/440 nm has widely been used as a marker for advanced glycation in studies of aging, diabetic complications and end-stage renal disease (ESRD). Diagnostic devices measuring skin autofluorescence at this wavelength revealed an association between fluorescence and cardiovascular morbidity and mortality. We now report the presence of a major fluorophore (LW-1) in human skin collagen which increases with age, diabetes and ESRD. It has a molecular weight of 623.2 Da, a UV maximum at 348 nm, and involves a lysine residue in an aromatic ring. LW-1 could not be synthesized...
Source: Archives of Biochemistry and Biophysics - October 29, 2009 Category: Biochemistry Authors: Sell DR, Nemet I, Monnier VM Tags: Arch Biochem Biophys Source Type: journals

Functional and Conformational Modulation of Human Cytochrome P450 1B1 by Anionic Phospholipids.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We investigated the interaction of human P450 1B1 (CYP1B1) with various phospholipid bilayers using the N-terminally deleted (Delta2-4)CYP1B1 and (Delta2-26)CYP1B1 enzymes. Among anionic phospholipids, phosphatidic acid (PA) and cardiolipin specifically increased the catalytic activities, membrane binding affinities, and thermal stabilities of both CYP1B1 proteins when phosphatidylcholine matrix was gradually replaced with these anionic phospholipids. PA- or cardiolipin- dependent changes of CYP1B1 conformation were revealed by altered Trp fluorescence and CD spectra. However, both PA and cardiolipin exerted more signi...
Source: Archives of Biochemistry and Biophysics - October 23, 2009 Category: Biochemistry Authors: Jang HH, Kim DH, Ahn T, Yun CH Tags: Arch Biochem Biophys Source Type: journals

Peroxisomal Localization and Function of NADP(+)-Specific Isocitrate Dehydrogenases in Yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Yeast peroxisomal NADP(+)-specific isocitrate dehydrogenase (IDP3) contains a canonical type I peroxisomal targeting sequence (a carboxyl-terminal Cys-Lys-Leu tripeptide), and provides the NADPH required for beta-oxidation of some fatty acids in that organelle. Cytosolic yeast IDP2 carrying a PTS1 (IDP2(+CKL)) was only partially localized to peroxisomes, and the enzyme was able to function in lieu of either peroxisomal IDP3 or cytosolic IDP2. The analogous isocitrate dehydrogenase enzyme (IDPA) from Aspergillus nidulans, irrespective of the presence or absence of a putative PTS1, was found to exhibit patterns of dual c...
Source: Archives of Biochemistry and Biophysics - October 22, 2009 Category: Biochemistry Authors: Lu Q, McAlister-Henn L Tags: Arch Biochem Biophys Source Type: journals

HflD, an Escherichia coli protein involved in the lambda lysis-lysogeny switch, impairs transcription activation by lambda CII.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The CII protein of bacteriophage lambda is the key regulator for the lytic-lysogenic choice of the viral lifecycle. An unstable homotetrameric transcription activator of the three phage promoters p(E), p(I) and p(aQ), lambda CII is stabilized by lambdaCIII and destabilized by the host protease, E. coli HflB (FtsH). In addition, other E. coli proteins HflK, HflC and HflD also influence lysogeny by acting upon CII. Among these, HflD (22.9 kDa), a peripheral membrane protein that is exposed towards the cytoplasm, interacts with CII and decreases the frequency of lysogenization of lambda by stimulating the degradation of C...
Source: Archives of Biochemistry and Biophysics - October 21, 2009 Category: Biochemistry Authors: Parua PK, Mondal A, Parrack P Tags: Arch Biochem Biophys Source Type: journals

A new factor Xa Inhibitor from Amblyomma cajennense with a unique domain composition.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bioactive compounds of great interest are found in the saliva of hematophagous organisms. While exploring a cDNA library derived from the salivary glands of the tick Amblyommacajennense, a transcript that codes for a protein with unique structure (containing an N-terminal Kunitz-type domain and a C-terminus with no homology to any annotated sequences) was found. The recombinant mature form of this protein ( approximately 13.5 kDa) was produced in E. coli BL21 (DE3), and it was able to inhibit Factor Xa (FXa) and extend global blood clotting times in vitro and ex vivo. Static and dynamic predictions of its tertiary stru...
Source: Archives of Biochemistry and Biophysics - October 21, 2009 Category: Biochemistry Authors: Batista IF, Ramos OH, Ventura JS, Junqueira-de-Azevedo IL, Ho PL, Chudzinski-Tavassi AM Tags: Arch Biochem Biophys Source Type: journals

Hydrodynamic and mass spectrometry analysis of nearly-intact human fibrinogen, chicken fibrinogen, and of a substantially monodisperse human fibrinogen fragment X.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The shape and solution properties of fibrinogen are affected by the location of the C-terminal portion of the Aalpha chains, which is presently still controversial. We have measured the hydrodynamic properties of a human fibrinogen fraction with these appendages mostly intact, of chicken fibrinogen, where they lack eleven characteristic thirteen-amino acids repeats, and of human fragment X, a plasmin early degradation product in which they have been removed. The human fibrinogen/fragmentX samples were extensively characterized by SDS-PAGE/Western blotting and mass spectrometry, allowing their composition to be precisel...
Source: Archives of Biochemistry and Biophysics - October 21, 2009 Category: Biochemistry Authors: Cardinali B, Profumo A, Aprile A, Byron O, Morris G, Harding SE, Stafford WF, Rocco M Tags: Arch Biochem Biophys Source Type: journals

Flavin-Containing Heme Enzymes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There are many examples of oxidative enzymes containing both flavin and heme prosthetic groups that carry out the oxidation of their substrate. For the purpose of this article we have chosen five systems. Two of these, the L-lactate dehydrogenase flavocytochrome b(2) and cellobiose dehydrogenase, carry out the catalytic chemistry at the flavin group. In contrast, the remaining three require activation of dioxygen at the heme group in order to accomplish substrate oxidation, these being flavohemoglobin, a nitric oxide dioxygenase, and the monooxygenases nitric oxide synthase and flavocytochrome P450 BM3, which functions...
Source: Archives of Biochemistry and Biophysics - October 19, 2009 Category: Biochemistry Authors: Mowat CG, Gazur B, Campbell LP, Chapman SK Tags: Arch Biochem Biophys Source Type: journals

The Conformation of End-Groups is One Determinant of Carotenoid Topology Suitable for High Fidelity Molecular Recognition: A Study of beta and epsilon-End-Groups.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conformation affects a carotenoid's ability to bind selectively to proteins. We calculated adiabatic energy profiles for rotating the ring end-groups around the C6-C7 bond and for flexing of the ring with respect to the polyene chain. The choice of computational methods is important. A low, 4.2 kcal/mol barrier to rotation exists for a beta-ring. An 8.3 kcal/mol barrier exists for rotation of an epsilon-ring. Rotation of the epsilon-ring is sensitive to substitution at C3. In the absence of external forces neither beta- nor epsilon- rings are rotationally constrained. The nearly parallel alignment of the beta-ring to t...
Source: Archives of Biochemistry and Biophysics - October 19, 2009 Category: Biochemistry Authors: Landrum JT, Chatfield DC, Mebel AA, Alvarez-Calderon F, Fernandez MV Tags: Arch Biochem Biophys Source Type: journals

Comparative study of HOCl-inflicted damage to bacterial DNA ex vivo and within cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The prospects for using bacterial DNA as an intrinsic probe for HOCl and secondary oxidants/chlorinating agents associated with it has been evaluated using both in vitro and in vivo studies. Single-strand and double-strand breaks occurred in bare plasmid DNA that had been exposed to high levels of HOCl, although these reactions were very inefficient compared to polynucleotide chain cleavage caused by the OH(*)-generating reagent, peroxynitrite. Plasmid nicking was not increased when intact Escherichia coli were exposed to HOCl; rather, the amount of recoverable plasmid diminished in a dose-dependent manner. At concentr...
Source: Archives of Biochemistry and Biophysics - October 19, 2009 Category: Biochemistry Authors: Suquet C, Warren JJ, Seth N, Hurst JK Tags: Arch Biochem Biophys Source Type: journals

Identification of hydrophobic amino acids required for lipid activation of C. elegans CTP:phosphocholine cytidylyltransferase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CTP:phosphocholine cytidylyltransferase (CCT), critical for phosphatidylcholine biosynthesis, is activated by translocation to the membrane surface. The lipid activation region of Caenorhabditis elegans CCT is between residues 246 and 266 of the 347 amino acid polypeptide, a region proposed to form an amphipathic alpha helix. When leucine 246, tryptophan 249, isoleucine 256, isoleucine 257, or phenylalanine 260, on the hydrophobic face of the helix, were changed individually to serine low activity was observed in the absence of lipid vesicles, similar to wild-type CCT, while lipid stimulated activity was reduced compar...
Source: Archives of Biochemistry and Biophysics - October 13, 2009 Category: Biochemistry Authors: Braker JD, Hodel KJ, Mullins DR, Friesen JA Tags: Arch Biochem Biophys Source Type: journals

Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Evidence suggests that a group of phytochemicals known as flavonoids are highly effective in reversing age-related declines in neuro-cognitive performance through their ability to interact with the cellular and molecular architecture of the brain responsible for memory and by reducing neuronal loss due to neurodegenerative processes. In particular, they may increase the number of, and strength of, connections between neurons, via their specific interactions with the ERK and Akt pathways, leading to an increase in neurotrophins such as BDNF. Concurrently, their effects on the peripheral and cerebral vascular system may ...
Source: Archives of Biochemistry and Biophysics - October 8, 2009 Category: Biochemistry Authors: Spencer JP, Vauzour D, Rendeiro C Tags: Arch Biochem Biophys Source Type: journals

Oligomeric interactions provide alternatives to direct steric modes of control of sugar kinase/actin/hsp70 superfamily functions by heterotropic allosteric effectors: Inhibition of E. coli glycerol kinase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Unlike those for monomeric superfamily members, heterotropic allosteric effectors of the tetrameric E. coli glycerol kinase (EGK) bind to only one of the two domains that define the catalytic cleft and far from the active site. An R369A amino acid substitution removes oligomeric interactions of a novel mini domain-swap loop of one subunit with the catalytic site of another subunit, and an A65T substitution perturbs oligomeric interactions in a second interface. Linked-functions enzyme kinetics, analytical ultracentrifugation, and FRET are used to assess effects of these substitutions on the allosteric control of cataly...
Source: Archives of Biochemistry and Biophysics - October 7, 2009 Category: Biochemistry Authors: Pettigrew DW Tags: Arch Biochem Biophys Source Type: journals

Interaction of LDS-751 with the drug-binding site of P-glycoprotein: a Trp fluorescence steady-state and lifetime study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
P-Glycoprotein (ABCB1) is an ATP-driven efflux pump which binds drugs within a large flexible binding pocket. Intrinsic Trp fluorescence was used to probe the interactions of LDS-751 (2-[4-(4-[dimethylamino]phenyl)-1,3-butadienyl]-3-ethylbenzo-thiazolium perchlorate) with purified P-glycoprotein, using steady-state/lifetime measurements and collisional quenching. The fast decay component of P-glycoprotein intrinsic fluorescence (tau(1) = 0.97 ns) was unaffected by LDS-751 binding, while the slow decay component (tau(2) = 4.02 ns) was quenched by dynamic and static mechanisms. Both the wavelength dependence of the decay...
Source: Archives of Biochemistry and Biophysics - October 6, 2009 Category: Biochemistry Authors: Lugo MR, Sharom FJ Tags: Arch Biochem Biophys Source Type: journals

Differential effects of non-steroidal anti-inflammatory drugs on mitochondrial dysfunction during oxidative stress.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We investigated the effects of several non-steroidal anti-inflammatory drugs on swelling related properties of mitochondria, with an emphasis on compounds that are marketed and utilized topically in the eye (nepafenac, ketorolac, diclofenac, bromfenac), and compared these to the effects of amfenac (a metabolite of nepafenac) and to celecoxib (active principle of Celebrex). With the exception of the last compound, none of the drugs promote swelling of normal mitochondria that are well energized by succinate oxidation. However, swelling is seen when the mitochondria are under an oxidative stress due to the presence of t-...
Source: Archives of Biochemistry and Biophysics - September 30, 2009 Category: Biochemistry Authors: Lal N, Kumar J, Erdahl WE, Pfeiffer DR, Gadd ME, Graff G, Yanni JM Tags: Arch Biochem Biophys Source Type: journals

Effect of high mobility group box-1 protein on apoptosis of peritoneal macrophages.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present study was performed to clarify the effects of high mobility group box-1 protein (HMGB1), a recently described late-acting pro-inflammatory cytokine, on apoptosis of macrophages. Treatment with HMGB1 (0.01, 0.1, 1, 10 mug/ml for 24 hours, or 10 mug/ml for 6, 12, 24, 48 hours) resulted in a dose- and time- dependent induction of apoptosis in mice macrophages, peaked at 24 hours after 10 mug/ml HMGB1 stimulation. HMGB1 treatment enhanced the receptor for advanced glycation endproducts (RAGE) expression and caspase-3 activation in macrophages. Blockage of RAGE and caspase-3 activation could significantly reduce...
Source: Archives of Biochemistry and Biophysics - September 29, 2009 Category: Biochemistry Authors: Zhu XM, Yao YM, Liang HP, Liu F, Dong N, Yu Y, Sheng ZY Tags: Arch Biochem Biophys Source Type: journals

Glycosaminoglycans reduced inflammatory response by modulating toll-like receptor-4 in lps-stimulated chondrocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lipopolysaccharide (LPS)-mediated activation of toll-like receptor-4 (TLR-4) complex induces specific signalling pathways, such as the myeloid differentiation primary response protein-88 (MyD88) and the tumor necrosis factor receptor-associated factor-6 (TRAF6), involving NF-kB activation. As previous data reported that hyaluronan (HA) and heparan sulphate (HS) may interact with TLR-4, the aim of this study was to investigate whether glycosaminoglycans (GAGs) may modulate the TLR-4 receptor in a model of LPS-induced inflammatory cytokines in mouse chondrocytes. LPS stimulation up-regulated all inflammation parameters. ...
Source: Archives of Biochemistry and Biophysics - September 29, 2009 Category: Biochemistry Authors: Campo GM, Avenoso A, Campo S, Traina P, D'Ascola A, Calatroni A Tags: Arch Biochem Biophys Source Type: journals

Structural and Biophysical Properties of Metal-Free Pathogenic SOD1 Mutants A4V and G93A.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the destruction of motor neurons in the spinal cord and brain. A subset of ALS cases are linked to dominant mutations in copper-zinc superoxide dismutase (SOD1). The pathogenic SOD1 variants A4V and G93A have been the foci of multiple studies aimed at understanding the molecular basis for SOD1-linked ALS. The A4V variant is responsible for the majority of familial ALS cases in North America, causing rapidly progressing paralysis once symptoms begin and the G93A SOD1 variant is overexpressed in often studied murine mod...
Source: Archives of Biochemistry and Biophysics - September 29, 2009 Category: Biochemistry Authors: Galaleldeen A, Strange R, Whitson LJ, Antonyuk S, Narayana N, Taylor AB, Schuermann JP, Holloway SP, Hasnain SS, Hart PJ Tags: Arch Biochem Biophys Source Type: journals

Stability and structure of the membrane protein transporter Ffh is modulated by substrates and lipids.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cytosolic protein Ffh transports membrane proteins from the ribosome to the inner membrane in complex with 4.5S RNA. Here we show that native Ffh binds to the hydrophobic probe ANS in a 1 Ffh:3 ANS stoichiometry, revealing a hydrophobic binding site. Thermal precipitation of Ffh is shifted upwards by approximately 10 degrees C by ANS or substrate protein, suggesting that the hydrophobic binding site makes the protein aggregation prone. Chemical denaturation confirm that Ffh is a rather unstable protein. 4.5S RNA destabilizes Ffh further, suggesting it keeps the protein in a more open conformation than the apoprotei...
Source: Archives of Biochemistry and Biophysics - September 29, 2009 Category: Biochemistry Authors: Reinau ME, Otzen DE Tags: Arch Biochem Biophys Source Type: journals

Hydrogen peroxide induced oxidation of peroxisomal malate synthase and catalase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Peroxisomes contain oxidases that produce H(2)O(2), which can result in protein oxidation. To test the vulnerability of peroxisomal proteins to oxidation in vivo the organelles were isolated from castor bean endosperm incubated with H(2)O(2). When peroxisomes were exposed to H(2)O(2)in vivo, the peroxisomal proteins exhibited an increase in carbonylation as detected in avidin blots of biotin hydrazide derivitized samples. Biotin tagged peptides from trypsin digests of the proteins were analyzed by mass spectroscopy and compared to the masses of peptides from the same protein that had not been biotin tagged and from pro...
Source: Archives of Biochemistry and Biophysics - September 29, 2009 Category: Biochemistry Authors: Anand P, Kwak Y, Simha R, Donaldson RP Tags: Arch Biochem Biophys Source Type: journals

Establishment and characterization of a novel method for evaluating gluconeogenesis using hepatic cell lines, H4IIE and HepG2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we attempted to establish a new method to evaluate gluconeogenesis using rat H4IIE hepatoma cells. High-density preculture and exposure to hypertonic solutions, which are known to upregulate the expression of gluconeogenic genes, enhanced glucose release (GR) promoted by gluconeogenic substrates (GS: 1 mM pyruvate and 10 mM lactate). Our method was also applicable to the human hepatoma HepG2 cells. Measurement of glycogen content in HepG2 cells revealed that GR was compensated by glycogenolysis in the basal state and was generated by gluconeogenesis in the presence of GS. The optimized conditions increased t...
Source: Archives of Biochemistry and Biophysics - September 28, 2009 Category: Biochemistry Authors: Okamoto T, Kanemoto N, Ban T, Sudo T, Nagano K, Niki I Tags: Arch Biochem Biophys Source Type: journals

The in vitro motility assay parameters of actin filaments from Mytilus edulis exposed in vivo to copper ions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
One important aspect of oxidative stress is chemical modification of lipids, proteins and nucleic acids. Copper has been shown to be one of the agents causing oxidative stress. In muscles copper binds to Cys 374 of the actin monomer and catalyzes interchain S-S bond formation in F-actin. The aim of the present work was to study the functional consequences of actin modifications, induced by copper treatment of Mytilus edulis in vivo, on the in vitro motility parameters of isolated actin filaments from foot and adductor muscles. CuCl(2) treatment reduced the sliding velocity of actin filaments extracted from foot muscle ...
Source: Archives of Biochemistry and Biophysics - September 27, 2009 Category: Biochemistry Authors: Vikhoreva NN, Vikhorev PG, Fedorova MA, Hoffmann R, Månsson A, Kuleva NV Tags: Arch Biochem Biophys Source Type: journals

Sphingosine Kinase 1 Localized to the Plasma Membrane Lipid Raft Microdomain Overcomes Serum Deprivation Induced Growth Inhibition.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, using multiple biochemical and subcellular fractionation techniques we demonstrate that endogenous SphK1 protein and its substrate, D-erythro sphingosine, are present within the PMLRM. Additionally, we demonstrate that the PMA stimulation of SphK1 localized to the PMLRM results in production of sphingosine-1-phosphate as well as induction of cell growth under serum-deprivation conditions. We further report that Ser225Ala and Thr54Cys mutations, reported to abrogate phosphatidylserine binding, block SphK1 targeting to the PMLRM and SphK1 induced cell growth. Together these findings provide direct evidence th...
Source: Archives of Biochemistry and Biophysics - September 22, 2009 Category: Biochemistry Authors: Hengst JA, Francy-Guilford JM, Fox TE, Wang X, Conroy EJ, Yun JK Tags: Arch Biochem Biophys Source Type: journals

P-glycoprotein (ABCB1) Modulates Collateral Sensitivity of a Multidrug Resistant Cell Line to Verapamil.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we expand on our earlier study and demonstrate that P-gp1 expression in drug resistant cells modulates collateral sensitivity. Using P-gp1-specific siRNA, P-gp1 expression in the multidrug resistant CH(R)C5 cells was significantly down-regulated beginning on day 2 post-transfection of siRNA. Furthermore, down-regulation of P-gp1 led to increased sensitivity of CH(R)C5 cells to paclitaxel and doxorubicin, but not to cis-platinum, due to inhibition of P-gp1 drug efflux pump. Down regulation of P-gp1 expression completely reversed collateral sensitivity to verapamil and two other drugs, progesterone and deoxyc...
Source: Archives of Biochemistry and Biophysics - September 18, 2009 Category: Biochemistry Authors: Laberge RM, Ambadipudi R, Georges E Tags: Arch Biochem Biophys Source Type: journals

Binding-equilibrium and kinetic studies of anthocyanidin reductase from Vitis vinifera.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anthocyanidin reductase from Vitis vinifera catalyzes an NADPH-dependent double reduction of anthocyanidins. At pH 7.5 and 30 degrees C, steady-state kinetics support a hyperbolic and rapid-equilibrium ordered mechanism, with NADPH binding first, K(M(cyan)) = 2.82 +/- 0.66 muM and K(i(NADPH)) = 111 +/- 23 muM. The chromatographic method of Hummel and Dreyer was used for binding-equilibrium studies of NADPH, NADP(+) and catechin, at pH 7. This confirmed hyperbolic binding of NADPH and NADP(+) to the free enzyme, with a single binding site each and with dissociation constants K(NADPH) = 45.9 +/- 2 muM and K(NADP)+ = 83 +...
Source: Archives of Biochemistry and Biophysics - September 18, 2009 Category: Biochemistry Authors: Gargouri M, Gallois B, Chaudière J Tags: Arch Biochem Biophys Source Type: journals

Kinetic Characterization and Quaternary Structure of Glutamate Racemase from the Periodontal Anaerobe Fusobacterium nucleatum.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cofactor-independent glutamate racemases (GRs) that supply the d-glutamate required for biosynthesis of the peptidoglycan that encapsulates bacterial cells are attractive targets for the development of antibacterial drugs. Recombinant GR from Fusobacterium nucleatum (FnGR), a Gram-negative anaerobe involved in periodontal disease, was overproduced, purified, and characterized. Unlike most other GRs, FnGR is a pseudosymmetric enzyme, catalyzing the racemization of glutamate enantiomers with similar kinetic parameters (k(cat)(l-->d) = 17.4+/-0.8 s(-1), K(m)(l-->d) = 1.04+/-0.07 mM, k(cat)(d-->l) = 26+/-1 s(-1), ...
Source: Archives of Biochemistry and Biophysics - September 18, 2009 Category: Biochemistry Authors: Potrykus J, Flemming J, Bearne SL Tags: Arch Biochem Biophys Source Type: journals

Triacylglycerol-induced impairment in mitochondrial biogenesis and function in J774.2 and mouse peritoneal macrophage foam cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, this study demonstrates the important role of mitochondrial biogenesis dysfunction in TG-induced lipotoxicity in macrophages. PMID: 19772854 [PubMed - as supplied by publisher] (Source: Archives of Biochemistry and Biophysics)
Source: Archives of Biochemistry and Biophysics - September 18, 2009 Category: Biochemistry Authors: Aronis A, Aharoni-Simon M, Madar Z, Tirosh O Tags: Arch Biochem Biophys Source Type: journals

Quinolinol and peptide inhibitors of zinc protease in botulinum neurotoxin A: effects of zinc ion and peptides on inhibition.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Quinolinol derivatives were found to be effective inhibitors of botulinum neurotoxin serotype A (BoNT/A). Studies of the inhibition and binding of 7-(phenyl(8-quinolinylamino)methyl)-8-quinolinol (QAQ) to the light chain domain (BoNT/A LC) showed that QAQ is a non-competitive inhibitor for the zinc protease activity. Binding and molecular modeling studies reavel that QAQ binds to a hydrophobic pocket near the active site. Its inhibitor effect does not involve the removal of zinc ion from the light chain. A 24-mer SNAP-25 peptide containing E183 to G206 with Q197C mutation (Peptide C) binds to BoNT/A LC with an unusuall...
Source: Archives of Biochemistry and Biophysics - September 18, 2009 Category: Biochemistry Authors: Lai H, Feng M, Roxas-Duncan V, Dakshanamurthy S, Smith LA, Yang DC Tags: Arch Biochem Biophys Source Type: journals

Role of naturally occurring osmolytes in protein folding and stability.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Osmolytes are typically accumulated in the intracellular environment at relatively high concentrations when cells/tissues are subjected to stress conditions. Osmolytes are common in a variety of organisms, including microorganisms, plants, and animals. They enhance thermodynamic stability of proteins by providing natively-folded conformations without perturbing other cellular processes. By burying the backbone into the core of folded proteins, osmolytes can provide significant stability to proteins. Two properties of osmolytes are particularly important: i) their ability to impart increased thermodynamic stability to f...
Source: Archives of Biochemistry and Biophysics - September 17, 2009 Category: Biochemistry Authors: Kumar R Tags: Arch Biochem Biophys Source Type: journals

ADAM8 Substrate Specificity: Influence of pH on Pre-processing and Proteoglycan Degradation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we demonstrate that an early critical autolytic event, we have termed pre-processing, is accelerated at acidic pH (pH 5.5) while autolytic activation is abrogated under the same conditions. Likewise, we found that pre-processing is hindered and autolytic activation is facilitated in neutral pH conditions, and thus demonstrates a pH-dependent shift in substrate selectivity. This finding is further supported by two peptide substrates corresponding to the pre-processing and C-terminal scissile bonds that were preferentially cleaved at acidic and neutral pH, respectively. Lastly, we found fibronectin cleavage t...
Source: Archives of Biochemistry and Biophysics - September 16, 2009 Category: Biochemistry Authors: Hall T, Pegg LE, Pauley AM, Fischer HD, Tomasselli AG, Zack MD Tags: Arch Biochem Biophys Source Type: journals

Kinetic and structural features of betaine aldehyde dehydrogenases: mechanistic and regulatory implications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The betaine aldehyde dehydrogenases (BADH; E.C. 1.2.1.8) are so called because they catalyze the irreversible NAD(P)(+)-dependent oxidation of betaine aldehyde to glycine betaine, which may function as (i) a very efficient osmoprotectant accumulated by both prokaryotic and eukaryotic organisms to cope with osmotic stress, (ii) a metabolic intermediate in the catabolism of choline in some bacteria such as the pathogen Pseudomonas aeruginosa, or (iii) a methyl donor for methionine synthesis. BADH enzymes can also use as substrates aminoaldehydes as well as other quaternary ammonium and tertiary sulfonium compounds, thus ...
Source: Archives of Biochemistry and Biophysics - September 16, 2009 Category: Biochemistry Authors: Muñoz-Clares RA, Díaz-Sánchez AG, González-Segura L, Montiel C Tags: Arch Biochem Biophys Source Type: journals

Rice Family GH1 Glycoside Hydrolases with beta-d-Glucosidase and beta-d-Mannosidase Activities.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Plant beta-d-mannosidases and a rice beta-d-glucosidase, Os3BGlu7, with weak beta-d-mannosidase activity, cluster together in phylogenetic analysis. To investigate the relationship between substrate specificity and amino acid sequence similarity in family GH1 glycoside hydrolases, Os3BGlu8 and Os7BGlu26, putative rice beta-d-glucosidases from this cluster, and a beta-d-mannosidase from barley (rHvBII), were expressed in Escherichia coli and characterized. Os3BGlu8, the amino acid sequence and molecular model of which are most similar to Os3BGlu7, hydrolysed 4-nitrophenyl- beta-d-glucopyranoside (4NPGlc) faster than 4-n...
Source: Archives of Biochemistry and Biophysics - September 16, 2009 Category: Biochemistry Authors: Kuntothom T, Luang S, Harvey AJ, Fincher GB, Opassiri R, Hrmova M, Cairns JR Tags: Arch Biochem Biophys Source Type: journals

In vitro metal uptake by recombinant human manganese superoxide dismutase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metal uptake by the antioxidant defense metalloenzyme manganese superoxide dismutase (MnSOD) is an essential step in the functional maturation of the protein that is just beginning to be investigated in detail. We have extended earlier in vitro studies on metal binding by the dimeric Escherichia coli apo-MnSOD to investigate the mechanism of metal uptake by tetrameric human and Thermus thermophilus apo-MnSODs. Like the E. coli apo-MnSOD, these proteins also bind metal ions in vitro in a thermally-activated, pH-sensitive process. However, metal uptake by the tetrameric apo-MnSODs exhibits a number of important differenc...
Source: Archives of Biochemistry and Biophysics - September 11, 2009 Category: Biochemistry Authors: Whittaker MM, Whittaker JW Tags: Arch Biochem Biophys Source Type: journals

Redox characterization of human cyclophilin D: identification of a new mammalian mitochondrial redox sensor ?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria are metabolically highly active cell organelles that are also implicated in reactive oxygen species production and in cell death regulation. Cyclophilin D, the only human mitochondrial isoform of cyclophilins, plays an essential role in the formation of the mitochondrial permeability transition pore leading to cell necrosis. Recently, it has been shown that redox environment modifies structural and functional properties of some plant cyclophilins. Here, it is shown that oxidation of human cyclophilin D influences the conformation of the enzyme but also its activity. Site-directed mutagenized variants of cy...
Source: Archives of Biochemistry and Biophysics - September 3, 2009 Category: Biochemistry Authors: Linard D, Kandlbinder A, Degand H, Morsomme P, Dietz KJ, Knoops B Tags: Arch Biochem Biophys Source Type: journals

Cordycepin causes p21WAF1-mediated G2/M cell cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has many pharmacological activities. The present study reveals novel molecular mechanisms for the anti-tumor effects of cordycepin in two different bladder cancer cell lines, 5637 and T-24 cells. Cordycepin treatment, at a dose of 200 M (IC(50)) during cell cycle progression resulted in significant and dose-dependent growth-inhibition, which was largely due to G2/M phase arrest, and resulted in an up-regulation of p21WAF1 expression, independent of the p53 pathway. Moreover, treatment with cordycepin induced phosphorylation of JNK (c-Jun N-ter...
Source: Archives of Biochemistry and Biophysics - September 2, 2009 Category: Biochemistry Authors: Lee SJ, Kim SK, Kim WJ, Moon SK Tags: Arch Biochem Biophys Source Type: journals

Inactivation of cystathionine beta-synthase with peroxynitrite.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study demonstrates the susceptibility of CBS to reactive oxygen/nitrogen species, with potential relevance to hyperhomocysteinemia, a risk factor for cardiovascular diseases. PMID: 19733148 [PubMed - as supplied by publisher] (Source: Archives of Biochemistry and Biophysics)
Source: Archives of Biochemistry and Biophysics - September 1, 2009 Category: Biochemistry Authors: Celano L, Gil M, Carballal S, Durán R, Denicola A, Banerjee R, Alvarez B Tags: Arch Biochem Biophys Source Type: journals

Prostaglandin h synthase: resolved and unresolved mechanistic issues.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cyclooxygenase and peroxidase activities of prostaglandin H synthase (PGHS)-1 and -2 have complex kinetics, with the cyclooxygenase exhibiting feedback activation by product peroxide and irreversible self-inactivation, and the peroxidase undergoing an independent self-inactivation process. The mechanistic bases for these complex, non-linear steady-state kinetics have been gradually elucidated by a combination of structure/function, spectroscopic and transient kinetic analyses. It is now apparent that most aspects of PGHS-1 and -2 catalysis can be accounted for by a branched chain mechanism involving a classic heme-...
Source: Archives of Biochemistry and Biophysics - August 30, 2009 Category: Biochemistry Authors: Kulmacz RJ, Tsai AL Tags: Arch Biochem Biophys Source Type: journals

Rational optimization of the DSL ligase ribozyme with GNRA/receptor interacting modules.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we have rationally designed and analyzed the catalytic and self-assembly properties of several trans-DSL ribozymes with different sets of natural and artificial GNRA-receptor clamps. Two variants newly designed in this study showed significantly enhanced catalytic properties with respect of the original trans-DSL construct. While this work allows dissection of the turnover and catalytic properties of the trans-DSL ribozyme, it also emphasizes the remarkable modularity of RNA tertiary structure for nano-construction of complex functions. PMID: 19728985 [PubMed - as supplied by publisher] (Source: Archives...
Source: Archives of Biochemistry and Biophysics - August 30, 2009 Category: Biochemistry Authors: Ishikawa J, Matsumura S, Jaeger L, Inoue T, Furuta H, Ikawa Y Tags: Arch Biochem Biophys Source Type: journals