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Irreversible inhibition of human cathepsins B, L, S and K by hypervalent tellurium compoundsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1205-1212 Abstract The inhibition of human cysteine cathepsins B, L, S and K was evaluated by a set of hypervalent tellurium compounds (telluranes) comprising both organic and inorganic derivatives. All telluranes studied showed a time- and concentration-dependent irreversible inhibition of the cathepsins, and their second-order inactivation rate constants were determined. The organic derivatives were potent inhibitors of the cathepsins and clear specificities were detected, which were parallel to their known substrate specificities. In all cases, the activity of the tellurane-inhibited cathe...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Placental expression of proteases and their inhibitors in patients with HELLP syndromeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1199-1204 Abstract In preeclampsia and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome, impaired trophoblast invasion and excessive fibrin deposition in the placental intervillous space is associated with fetal compromise. However, little information is available whether modulation of placental protease expression – potentially causing impaired trophoblast invasion – is associated with the HELLP syndrome. Total RNA and protein were extracted from placental tissue from 11 females with HELLP syndrome and 8 controls matched for gestational age. mRNA expression of matrix m...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts – a bioinformatical analysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1185-1197 Abstract In genome-wide screens we studied CA/C1 peptidases of malaria-causing plasmodia and their hosts (man and mouse). For Plasmodium falciparum and P. berghei, several new CA/C1 peptidase genes encoding proteases of the L- and B-family with specific promoter modules were identified. In addition, two new human CA/C1 peptidase loci and one new mouse gene locus were found; otherwise, the sets of CA/C1 peptidase genes in man and mouse seem to be complete now. In each species studied there is a multitude of CA/C1 peptidases with lysosomal localization signals and partial functional o...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Plasmodium falciparum glyoxalase II: Theorell-Chance product inhibition patterns, rate-limiting substrate binding via Arg257/Lys260, and unmasking of acid-base catalysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1171-1183 Abstract Glyoxalase II (GloII) is a ubiquitous thioester hydrolase catalyzing the last step of the glutathione-dependent conversion of 2-oxoaldehydes to 2-hydroxycarboxylic acids. Here, we present a detailed structure-function analysis of cGloII from the malaria parasite Plasmodium falciparum. The activity of the enzyme was salt-sensitive and pH-log kcat and pH-log kcat/Km profiles revealed acid-base catalysis. An acidic pKaapp value of approximately 6 probably reflects hydroxide formation at the metal center. The glutathione-binding site was analyzed by site-directed mutagenesis. S...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Structural analysis of the choline-binding protein ChoX in a semi-closed and ligand-free conformationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here the crystal structure of ChoX in an unusual, ligand-free conformation that represents a semi-closed form of ChoX. The analysis revealed a subdomain movement in the N-lobe of ChoX. Comparison with the two well-characterized substrate binding proteins, MBP and HisJ, suggests the presence of a similar subdomain in these proteins. (Source: Biological Chemistry)
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Mechanism of activation of Saccharomyces cerevisiae calcineurin by Mn2+Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that the in vitro phosphatase reaction activated by Mn2+ typically has a pronounced initial lag phase caused by slow conformational rearrangement of the holoenzyme-Mn2+. A similar lag phase was detected using just the catalytic domain of yeast CN, indicating that the slowness of Mn2+-induced conformational change of CN results from a rearrangement within the catalytic domain. The Mn2+-activation of CN was reversible. The dissociation constant of the CN heterodimer containing the CNA2 subunit in the presence of Mn2+ was 3-fold higher than that of CN containing the CNA1 subunit and that of the catalytic domains of ...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

The epigenetic bottleneck of neurodegenerative and psychiatric diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1145-1153 Abstract The orchestrated expression of genes is essential for the development and survival of every organism. In addition to the role of transcription factors, the availability of genes for transcription is controlled by a series of proteins that regulate epigenetic chromatin remodeling. The two most studied epigenetic phenomena are DNA methylation and histone-tail modifications. Although a large body of literature implicates the deregulation of histone acetylation and DNA methylation with the pathogenesis of cancer, recently epigenetic mechanisms have also gained much attention in...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Dissection of gene regulatory networks in embryonic stem cells by means of high-throughput sequencingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1139-1144 Abstract Transcription factor regulation of gene expression and chromatin-controlled epigenetic memory systems are closely cooperating in establishing the pluripotent state of embryonic stem (ES) cells and maintaining cell fate decisions throughout development of an organism. A thorough understanding of the regulatory transcriptional circuitry that rules the underlying plastic yet heritable gene expression programs in ES cells is of great importance. With the advent of next-generation sequencing technologies facilitating the quantitative assessment of functional genomics assays it i...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Memory and neural networks on the basis of color centers in solidsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1133-1138 Abstract Optical data recording is one of the most widely used and efficient systems of memory in the non-living world. The application of color centers in this context offers not only systems of high speed in writing and read-out due to a high degree of parallelism in data handling but also a possibility to set up models of neural networks. In this way, systems with a high potential for image processing, pattern recognition and logical operations can be constructed. A limitation to storage density is given by the diffraction limit of optical data recording. It is shown that this li...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Ultrafast memory loss and relaxation processes in hydrogen-bonded systemsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1125-1132 Abstract Structural memory of aqueous systems, such as neat water and biomolecules, in an aqueous environment is strongly influenced by hydrogen bond dynamics. Vibrational spectroscopy in the femtosecond (fs) time domain is applied to map structural dynamics in real-time and identify underlying molecular interactions. Neat liquid water displays an ultrafast loss of structural memory with the fastest decay of structural correlations occurring in the sub-100 fs regime. Both OH stretching and bending excitations of water molecules decay on a subpicosecond time scale, followed by dissi...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Balance of power – dynamic regulation of chromatin in plant developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1113-1123 Abstract Chromatin states profoundly determine and maintain gene activity and gene repression in eukaryotic organisms. Regulation of chromatin involves chromatin remodeling, chromatin modifications and exchange of chromatin components and is linked to DNA methylation in some cases. In plants and other organisms, chromatin proteins control many developmental pathways, integrate changes in the environment and can confer a cellular memory of these cues. Here, we review the molecular mechanisms that provide a dynamic regulation of chromatin in a cell. In addition, we discuss how chromat...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Mechanistic insights in light-induced cAMP production by photoactivated adenylyl cyclase alpha (PACα)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1105-1111 Abstract The flagellate Euglena gracilis contains as photoreceptor complex a heterotetrameric light-sensitive adenylyl cyclase (AC), consisting of the flavoproteins PACα and PACβ. Previously, we demonstrated the functional expression of PACα and PACβ in oocytes from Xenopus laevis and of PACα in different animal cell types. Both yielded a blue light-induced increase of cellular [cAMP]. Here, we report that the action spectrum of PACα is flavoprotein-typical, with maxima at ∼380 and ∼470 nm. Mutational analysis of PACα yields a model for its structure and function. PACα s...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Chemotaxis: how bacteria use memoryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1097-1104 Abstract Bacterial chemotaxis represents one of the simplest and best studied examples of unicellular behavior. Chemotaxis allows swimming bacterial cells to follow chemical gradients in the environment by performing temporal comparisons of ligand concentrations. The process of chemotaxis in the model bacterium Escherichia coli has been studied in great molecular detail over the past 40 years, using a large range of experimental tools to investigate physiology, genetics and biochemistry of the system. The abundance of quantitative experimental data enabled detailed computational mo...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Protein carboxyl methylation and the biochemistry of memoryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1087-1096 Abstract Bacterial chemotaxis is mediated by two reversible protein modification chemistries: phosphorylation and carboxyl methylation. Attractants bind to membrane chemoreceptors that control the activity of a protein kinase which acts in turn to control flagellar motor activity. Coordinate changes in receptor carboxyl methylation provide a negative feedback mechanism that serves a memory function. Protein carboxyl methylation might play an analogous role in the nervous system. Two protein carboxyl methyltransferases serve to regulate signal transduction pathways in eukaryotic cell...
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Highlight: Molecular and Cellular Mechanisms of MemoryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (11): 1085-1085 No abstract available (Source: Biological Chemistry)
Source: Biological Chemistry - October 6, 2009 Category: Chemistry Source Type: journals

Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 1079-1083 Abstract The different activities of the tumor suppressor p53 are tightly regulated by various negative and positive feedback loops, which allow accurate control of its function. Here we show that the p53-inducible ubiquitin E3 ligase Siah-1L can bind to the p53 phosphorylating kinase HIPK2 and thus allows its ubiquitination and proteasomal elimination. Siah-1L also eliminates the HIPK family member HIPK3, indicating that its activity is not restricted to one member of the HIPK family. The stimulating effect of HIPK2 on p53-triggered transcription is counteracted by Siah-1L, thus sh...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 1063-1077 Abstract RhoA and RhoC are highly related Rho GTPases, but differentially control cellular behaviour. We combined molecular, cellular, and biochemical experiments to characterise differences between these highly similar GTPases. Our findings demonstrate that enhanced expression of RhoC results in a striking increase in the migration and invasion of pancreatic carcinoma cells, whereas forced expression of RhoA decreases these actions. These isoform-specific functions correlate with differences in the cellular activity of RhoA and RhoC in human cells, with RhoC being more active than ...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase AEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 1057-1061 Abstract We identified a molten globule-like intermediate of 2,5-diketo-d-gluconate reductase A (DKGR) at pH 2.5, which has a prominent β-sheet structure. The molten globule state of the protein shows amyloidogenic property >50 μm protein concentration. Interestingly, a 1:1 molar ratio of curcumin prevents amyloid formation as shown by the Thioflavin-T assay and atomic force microscopy. To the best of our knowledge, this is the first report on amyloid formation by an (α/β)8-barrel protein. The results presented here indicate that the molten globule state has an important role i...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Hepatic differentiation of pluripotent stem cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 1047-1055 Abstract In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in l...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

The chemokine scavenging receptor D6 limits acute toxic liver injury in vivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, the chemokine scavenger receptor D6 has a non-redundant role in acute toxic liver injury in vivo. These results support the importance of post-translational chemokine regulation and describe a new mechanism of immune modulation within the liver. (Source: Biological Chemistry)
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Epidermal growth factor receptor signaling in liver cell proliferation and apoptosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article summarizes recent findings on the molecular mechanisms involved in EGFR-mediated cell proliferation and apoptosis. The emphasis is on the interplay between EGFR and CD95 (Fas, APO-1) death receptor-signaling, which is determined by the signaling context and liver cell type investigated. (Source: Biological Chemistry)
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Interplay between host cell and hepatitis C virus in regulating viral replicationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 1013-1032 Abstract Viral life cycle as that of the hepatitis C virus (HCV) completely relies on host cell infrastructure, presupposing that the virus has evolved mechanisms to utilize and control all cellular molecules or pathways required for viral life cycle. Hence, HCV must have acquired the ability to gain access to key pathways controlling processes, such as cell growth, apoptosis and protein synthesis, which are all considered to also be crucial for liver regeneration. This occurs in a balanced way permitting persistent replication of viral genomes and production of infectious particles...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Hepatic and pancreatic stellate cells in focusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 1003-1012 Abstract Stellate cells are vitamin A-storing cells of liver and pancreas and have been described in all vertebrates ranging from lampreys (primitive fish) to humans, demonstrating their major importance. This cell type is thought to contribute to fibrosis, a condition characterized by an excess deposition of extracellular matrix proteins. Recently, the expression of stem/progenitor cell markers, such as CD133 (prominin-1) and Oct4, was discovered in hepatic stellate cells (HSCs) of rats. Moreover, HSCs possess signaling pathways important for maintenance of stemness and cell differ...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Cellular plasticity of the pancreasEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 995-1001 Abstract Cell replacement therapy holds promises for treatment of patients suffering from diabetes mellitus. When determining the appropriate strategies to amplify the amount of transplantable β-cells, sufficient knowledge of the developmental programs regulating β-cell differentiation is crucial. Here, we describe the plasticity of the different pancreatic cell types in vivo and in vitro and their potential to serve as β-cell progenitor. (Source: Biological Chemistry)
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Ancestral vascular tube formation and its adoption by tumorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 985-994 Abstract Similar to growing and metabolically active tissues, tumors require a dense vasculature to gain access to oxygen and nutrients. However, blood vessels in tumors differ from vessels in normal tissues in many respects. In particular, the tumor vasculature is in an active state of angiogenesis or vasculogenesis, and it is immature and leaky. Blood vessels are multicellular tubes formed by polarized endothelial cells, which face the patent vascular lumen with their apical cell surface, whereas their basal cell surface faces extracellular matrix on the outside of the vessels. The ...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Immunologic hurdles of therapeutic stem cell transplantationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 977-983 Abstract Detailed knowledge of the immunologic properties of embryonic stem (ES) cells is a prerequisite for safe applications of ES cell-based regenerative medicine. Recently, the long-standing assumption that ES cells are ignored by immunocompetent hosts was disproved. Instead, it is becoming increasingly clear that ES cells actively protect themselves via several immunomodulatory and immunoevasive mechanisms against cytotoxic T-lymphocytes and natural killer cells. Here we review current knowledge about the immunologic properties of ES cells and discuss the implications for ES cell...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathwaysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 965-976 Abstract The liver plays a central role in the transformation and degradation of endogenous and exogenous chemicals, and in the removal of unwanted cells such as damaged, genetically mutated and virus-infected cells. Because of this function, the liver is susceptible to toxicity caused by the products generated during these natural occurrences. Hepatocyte death is the major feature of liver injury. In response to liver injury, specific intracellular processes are initiated to maintain liver integrity. Inflammatory cytokines including tumor necrosis factor (TNF)α and interleukin-6 (IL...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

The do's and don'ts of p53 isoformsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 951-963 Abstract Upon DNA damage and other stresses, the transcription factor p53 elicits numerous responses including DNA repair, cell cycle arrest and apoptosis, properties that make p53 the prototype tumor suppressor. In addition, p53 also transactivates genes whose products act in an anti-apoptotic manner providing strong evidence that p53 exhibits both tumor suppressive and tumorigenic functions. Although several events were postulated to contribute to the p53-mediated decision process, the precise mechanism(s) that governs p53 activities is still elusive. Recently, it was found that the...
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Highlight: ‘Regenerative Hepatology’Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (10): 949-950 No abstract available (Source: Biological Chemistry)
Source: Biological Chemistry - September 18, 2009 Category: Chemistry Source Type: journals

Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available toolsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 941-948 Abstract Cathepsin K (Cat K) degrades bone type I collagen and is a target for the pharmacological treatment of osteoporosis. Further roles for Cat K have been recently described, some of which are supported by the use of purportedly selective Cat K inhibitors in human and rodent cell-based assays. Twelve commercial and non-commercial Cat K inhibitors were profiled against a panel of purified human, rat, and mouse cysteine cathepsins and in two cell-based enzyme occupancy assays for activity against Cat K, B, and L. Ten inhibitors, including the carbohydrazide Cat K inhibitor II (Boc-P...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Catalytic properties of recombinant dipeptidyl carboxypeptidase from Escherichia coli: a comparative study with angiotensin I-converting enzymeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 931-940 Abstract Dipeptidyl carboxypeptidase from Escherichia coli (EcDcp) is a zinc metallopeptidase with catalytic properties closely resembling those of angiotensin I-converting enzyme (ACE). However, EcDcp and ACE are classified in different enzyme families (M3 and M2, respectively) due to differences in their primary sequences. We cloned and expressed EcDcp and studied in detail the enzyme's S3 to S1′ substrate specificity using positional-scanning synthetic combinatorial (PS-SC) libraries of fluorescence resonance energy transfer (FRET) peptides. These peptides contain ortho-aminobenzo...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Association between kallikrein-related peptidases (KLKs) and macroscopic indicators of semen analysis: their relation to sperm motilityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, the expression level of several seminal plasma KLKs correlates with liquefaction and viscosity indicators of semen quality and may aid in their differential diagnosis and etiology. (Source: Biological Chemistry)
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Advanced glycation end product accumulation in rho0 cells without a functional respiratory chainEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 915-919 Abstract Advanced glycation end products (AGEs) accumulate during ageing with reactive oxygen species from the mitochondrial respiratory chain discussed as a driving force. To determine the role of mitochondrial activity for AGE formation, a rho0 derivative of the 143B.TK- osteosarcoma cell line lacking the respiratory chain, was analysed. These cells exhibit decreased superoxide formation but unchanged mitochondrial SOD expression as well as unchanged antioxidative free sulfhydryl (SH) levels. Whereas total protein content shows no differences in AGE levels, cell fractionation and Wes...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Cross talk between kinin and angiotensin II receptors in mouse abdominal aortaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 907-913 Abstract Bradykinin (BK) is a vasorelaxant, algesic and inflammatory agent. Angiotensin II (AngII) is known to control vascular tone and promote growth, inflammation and artherogenesis. There is evidence for cross talking between BK and AngII receptors. Therefore, the effect of lack of kinin receptors was assessed in mice with genetic disruption of B1 or B2 and both receptors. Responsiveness of abdominal aortic rings to BK and AngII as well as the receptor gene expression of both peptides were analysed. Although no specific phenotype was displayed in the normotensive and healthy mice l...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

The effect of endogenous preproneuropeptide Y leucine 7 to proline 7 polymorphism on growth and apoptosis in primary cultured HUVECsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 899-905 Abstract Neuropeptide Y (NPY) is a universally expressed neuropeptide involved in the regulation of several physiological functions. The rather common leucine7 to proline7 (L7P) polymorphism in the signal peptide of preproNPY is a functional substitution, which changes the processing and release of NPY in cells. The mutation is associated with altered lipid levels and accelerated atherosclerosis in humans. Based on previous studies, we investigated the effect of the Pro7 allele in endothelial cells, which are known to play a role in the development of atherosclerosis. Cell proliferatio...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Peritumoral administration of GPI-anchored TIMP-1 inhibits colon carcinoma growth in Rag-2 γ chain-deficient miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 893-897 Abstract Exogenous application of recombinant TIMP-1 protein modified by addition of a glycosylphosphatidylinositol (GPI) anchor allows efficient insertion of the fusion protein into cell membranes. This ‘cell surface engineering’ leads to changes in the proteolytic environment. TIMP-1-GPI shows enhanced as well as novel in vitro biological activities including suppression of proliferation, reduced migration, and inhibition of invasion of the colon carcinoma cell line SW480. Treatment of SW480 tumors implanted in Rag (-/-) common γ chain (-/-) C57BL/6 mice with peritumorally appli...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

A dual role of the N-terminal FQQI motif in GLUT4 traffickingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 883-892 Abstract In adipocytes, the glucose transporter GLUT4 recycles between intracellular storage vesicles and the plasma membrane. GLUT4 is internalized by a clathrin- and dynamin-dependent mechanism, and sorted into an insulin-sensitive storage compartment. Insulin stimulation leads to GLUT4 accumulation on the cell surface. The N-terminal F5QQI motif in GLUT4 has been shown previously to be required for sorting of the protein in the basal state. Here, we show that the FQQI motif is a binding site for the medium chain adaptin μ1, a subunit of the AP-1 adaptor complex that plays a role in...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Metzincin's canonical methionine is responsible for the structural integrity of the zinc-binding siteEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 875-881 Abstract The metzincins constitute a subclan of metalloproteases possessing a HEXXHXXGXXH/D zinc-binding consensus sequence where the three histidines are zinc ligands and the glutamic acid is the catalytic base. A completely conserved methionine is located downstream of this motif. Families of the metzincin clan comprise, besides others, astacins, adamalysins proteases, matrix metallo-proteases, and serralysins. The latter are extracellular 50 kDa proteases secreted by Gram-negative bacteria via a type I secretion system. While there is a large body of structural and biochemical info...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

A soluble form of ammonia monooxygenase in Nitrosomonas europaeaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study shows that AMO resides in the cytoplasm of the bacteria in addition to its location in the membrane and is distributed approximately equally in both subcellular fractions. AMO in both fractions catalyzes the oxidation of ammonia and binds [14C]acetylene, a mechanism-based inhibitor which specifically interacts with catalytically active AMO. Soluble AMO was purified 12-fold to electrophoretic homogeneity with a yield of 8%. AMO has a molecular mass of approximately 283 kDa with subunits of ca. 27 kDa (α-subunit, AmoA), ca. 42 kDa (β-subunit, AmoB), and ca. 24 kDa (γ-subunit, cytochrome c1) in an α3β3γ3 ...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Effect of a quaternary pentamine on RNA stabilization and enzymatic methylationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 851-861 Abstract Extreme thermophiles produce unusually long polyamines, including the linear caldopentamine (Cdp) and the branched pentamine tetrakis(3-aminopropyl)-ammonium (Taa), with the latter containing a central quaternary ammonium moiety. Here we compare the interaction of these two pentamines with RNA by studying the heat denaturation, electrophoretic behavior, and ability of tRNA to be methylated in vitro by purified tRNA methyltransferases under various salt conditions. At concentrations in the micromolar range, branched Taa causes a considerable increase in the melting temperature ...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Induced human pluripotent stem cells: promises and open questionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 845-849 Abstract Adult cells have been reprogrammed into induced pluripotent stem (iPS) cells by introducing pluripotency-associated transcription factors. Here, we discuss recent advances and challenges of in vitro reprogramming and future prospects of iPS cells for their use in diagnosis and cell therapy. The generation of patient-specific iPS cells for clinical application requires alternative strategies, because genome-integrating viral vectors may cause insertional mutagenesis. Moreover, when suitable iPS cell lines will be available, efficient and selective differentiation protocols are ...
Source: Biological Chemistry - September 1, 2009 Category: Chemistry Source Type: journals

Dimeric/oligomeric DNA methyltransferases: an unfinished storyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (9): 835-844 Abstract DNA methyltransferases (MTases) are enzymes that carry out post-replicative sequence-specific modifications. The initial experimental data on the structure and kinetic characteristics of the EcoRI MTase led to the paradigm that type II systems comprise dimeric endonucleases and monomeric MTases. In retrospect, this was logical because, while the biological substrate of the restriction endonuclease is two-fold symmetrical, the in vivo substrate for the MTase is generally hemi-methylated and, hence, inherently asymmetric. Thus, the paradigm was extended to include all DNA MTases...
Source: Biological Chemistry - August 31, 2009 Category: Chemistry Source Type: journals

NMR and EPR studies of membrane transportersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 815-834 Abstract In order to fulfill their function, membrane transport proteins have to cycle through a number of conformational and/or energetic states. Thus, understanding the role of conformational dynamics seems to be the key for elucidation of the functional mechanism of these proteins. However, membrane proteins in general are often difficult to express heterologously and in sufficient amounts for structural studies. It is especially challenging to trap a stable energy minimum, e.g., for crystallographic analysis. Furthermore, crystallization is often only possible by subjecting the pro...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

The nanodisc: a novel tool for membrane protein studiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 805-814 Abstract A major challenge in the research on membrane-anchored and integral membrane protein complexes is to obtain these in a functionally active, water-soluble, and monodisperse form. This requires the incorporation of the membrane proteins into a native-like membrane or detergent micelle that mimics the properties of the original biological membrane. However, solubilization in detergents or reconstitution in liposomes or supported monolayers sometimes suffers from loss of activity and problematic analyses due to heterogeneity and aggregation. A developing technology termed nanodisc...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

Protein-lipid interactions: paparazzi hunting for snap-shotsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 795-803 Abstract Photoactivatable groups meeting the criterion of minimal perturbance allow the investigation of interactions in biological samples. Here, we review the application of photoactivatable groups in lipids enabling the study of protein-lipid interactions in (biological) membranes. The chemistry of various photoactivatable groups is summarized and the specificity of the interactions detected is discussed. The recent introduction of ‘click chemistry’ in photocrosslinking of membrane proteins by photo-activatable lipids opens new possibilities for the analysis of crosslinked produ...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

The peptide-loading complex – antigen translocation and MHC class I loadingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 783-794 Abstract A large and dynamic membrane-associated machinery orchestrates the translocation of antigenic peptides into the endoplasmic reticulum (ER) lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. The peptide-loading complex ensures that only high-affinity peptides, which guarantee long-term stability of MHC I complexes, are presented to T-lymphocytes. Adaptive immunity is dependent on surface display of the cellular proteome in the form of protein fragments, thus allowing efficient recognition of infected or malignant transformed cells. In th...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

Protein targeting by the signal recognition particleEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 775-782 Abstract Protein targeting by the signal recognition particle (SRP) is universally conserved and starts with the recognition of a signal sequence in the context of a translating ribosome. SRP54 and FtsY, two multidomain proteins with guanosine triphosphatase (GTPase) activity, are the central elements of the SRP system. They have to coordinate the presence of a signal sequence with the presence of a vacant translocation channel in the membrane. For coordination the two GTPases form a unique, nearly symmetric heterodimeric complex in which the activation of GTP hydrolysis plays a key ro...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disordersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 761-773 Abstract ZMPSTE24 is an integral membrane zinc metalloprotease originally discovered in yeast as an enzyme (called Ste24p) required for maturation of the mating pheromone a-factor. Surprisingly, ZMPSTE24 has recently emerged as a key protease involved in human progeroid disorders. ZMPSTE24 has only one identified mammalian substrate, the precursor of the nuclear scaffold protein lamin A. ZMPSTE24 performs a critical endoproteolytic cleavage step that removes the hydrophobic farnesyl-modified tail of prelamin A. Failure to do so has drastic consequences for human health and longevity. H...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

On the fate of early endosomesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 753-759 Abstract Proteins are endocytosed by various pathways into the cell. All these pathways converge at the level of the early endosome. The fate of the early endosome and how proteins are sorted into recycling and late endosomes/multi-vesicular body is a matter of debate and intense research. Obviously, the transition from early to late endosome poses an interesting logistic problem and would merit attention on an intellectual level. Numerous diseases are also caused by defects in turning off/over signaling molecules or mis-sorting of proteins at the level of the early endosome. This brie...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals

Protein transport across the peroxisomal membraneEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biological Chemistry 390 (8): 745-751 Abstract The maintenance of peroxisome function depends on the formation of the peroxisomal membrane and the subsequent import of both membrane and matrix proteins. Without exception, peroxisomal matrix proteins are nuclear encoded, synthesized on free ribosomes and subsequently imported post-translationally. In contrast to other translocation systems that transport unfolded polypeptide chains, the peroxisomal import apparatus can facilitate the transport of folded and oligomeric proteins across the peroxisomal membrane. The peroxisomal protein import is mediated by cycling receptors t...
Source: Biological Chemistry - August 6, 2009 Category: Chemistry Source Type: journals