Thiol dioxygenases: from structures to functions
Trends Biochem Sci. 2024 Apr 15:S0968-0004(24)00073-2. doi: 10.1016/j.tibs.2024.03.007. Online ahead of print.ABSTRACTThiol oxidation to dioxygenated sulfinic acid is catalyzed by an enzyme family characterized by a cupin fold. These proteins act on free thiol-containing molecules to generate central metabolism precursors and signaling compounds in bacteria, fungi, and animal cells. In plants and animals, they also oxidize exposed N-cysteinyl residues, directing proteins to proteolysis. Enzyme kinetics, X-ray crystallography, and spectroscopy studies prompted the formulation and testing of hypotheses about the mechanism of...
Source: Trends in Biochemical Sciences - April 15, 2024 Category: Biochemistry Authors: Monica Perri Francesco Licausi Source Type: research

Thiol dioxygenases: from structures to functions
Trends Biochem Sci. 2024 Apr 15:S0968-0004(24)00073-2. doi: 10.1016/j.tibs.2024.03.007. Online ahead of print.ABSTRACTThiol oxidation to dioxygenated sulfinic acid is catalyzed by an enzyme family characterized by a cupin fold. These proteins act on free thiol-containing molecules to generate central metabolism precursors and signaling compounds in bacteria, fungi, and animal cells. In plants and animals, they also oxidize exposed N-cysteinyl residues, directing proteins to proteolysis. Enzyme kinetics, X-ray crystallography, and spectroscopy studies prompted the formulation and testing of hypotheses about the mechanism of...
Source: Trends in Biochemical Sciences - April 15, 2024 Category: Biochemistry Authors: Monica Perri Francesco Licausi Source Type: research

Taming AID mutator activity in somatic hypermutation
Trends Biochem Sci. 2024 Apr 12:S0968-0004(24)00077-X. doi: 10.1016/j.tibs.2024.03.011. Online ahead of print.ABSTRACTActivation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by introducing base substitutions into antibody genes, a process enabling antibody affinity maturation in immune response. How a mutator is tamed to precisely and safely generate programmed DNA lesions in a physiological process remains unsettled, as its dysregulation drives lymphomagenesis. Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, rest...
Source: Trends in Biochemical Sciences - April 13, 2024 Category: Biochemistry Authors: Yining Qin Fei-Long Meng Source Type: research

Hypoxia research, where to now?
Trends Biochem Sci. 2024 Apr 9:S0968-0004(24)00074-4. doi: 10.1016/j.tibs.2024.03.008. Online ahead of print.ABSTRACTInvestigating how cells and organisms sense and respond to O2 levels is essential to our understanding of physiology and pathology. This field has advanced considerably since the discovery of the major transcription factor family, hypoxia-inducible factor (HIF), and the enzymes that control its levels: prolyl hydroxylases (PHDs). However, with its expansion, new complexities have emerged. Herein we highlight three main areas where, in our opinion, the research community could direct some of their attention. ...
Source: Trends in Biochemical Sciences - April 10, 2024 Category: Biochemistry Authors: Brian M Ortmann Cormac T Taylor Sonia Rocha Source Type: research

Hypoxia research, where to now?
Trends Biochem Sci. 2024 Apr 9:S0968-0004(24)00074-4. doi: 10.1016/j.tibs.2024.03.008. Online ahead of print.ABSTRACTInvestigating how cells and organisms sense and respond to O2 levels is essential to our understanding of physiology and pathology. This field has advanced considerably since the discovery of the major transcription factor family, hypoxia-inducible factor (HIF), and the enzymes that control its levels: prolyl hydroxylases (PHDs). However, with its expansion, new complexities have emerged. Herein we highlight three main areas where, in our opinion, the research community could direct some of their attention. ...
Source: Trends in Biochemical Sciences - April 10, 2024 Category: Biochemistry Authors: Brian M Ortmann Cormac T Taylor Sonia Rocha Source Type: research

Hypoxia research, where to now?
Trends Biochem Sci. 2024 Apr 9:S0968-0004(24)00074-4. doi: 10.1016/j.tibs.2024.03.008. Online ahead of print.ABSTRACTInvestigating how cells and organisms sense and respond to O2 levels is essential to our understanding of physiology and pathology. This field has advanced considerably since the discovery of the major transcription factor family, hypoxia-inducible factor (HIF), and the enzymes that control its levels: prolyl hydroxylases (PHDs). However, with its expansion, new complexities have emerged. Herein we highlight three main areas where, in our opinion, the research community could direct some of their attention. ...
Source: Trends in Biochemical Sciences - April 10, 2024 Category: Biochemistry Authors: Brian M Ortmann Cormac T Taylor Sonia Rocha Source Type: research

RNA-DNA triplexes: molecular mechanisms and functional relevance
Trends Biochem Sci. 2024 Apr 5:S0968-0004(24)00075-6. doi: 10.1016/j.tibs.2024.03.009. Online ahead of print.ABSTRACTInteractions of RNA with DNA are principles of gene expression control that have recently gained considerable attention. Among RNA-DNA interactions are R-loops and RNA-DNA hybrid G-quadruplexes, as well as RNA-DNA triplexes. It is proposed that RNA-DNA triplexes guide RNA-associated regulatory proteins to specific genomic locations, influencing transcription and epigenetic decision making. Although triplex formation initially was considered solely an in vitro event, recent progress in computational, biochemi...
Source: Trends in Biochemical Sciences - April 6, 2024 Category: Biochemistry Authors: Matthias S Leisegang Timothy Warwick Julia St ötzel Ralf P Brandes Source Type: research

RNA-DNA triplexes: molecular mechanisms and functional relevance
Trends Biochem Sci. 2024 Apr 5:S0968-0004(24)00075-6. doi: 10.1016/j.tibs.2024.03.009. Online ahead of print.ABSTRACTInteractions of RNA with DNA are principles of gene expression control that have recently gained considerable attention. Among RNA-DNA interactions are R-loops and RNA-DNA hybrid G-quadruplexes, as well as RNA-DNA triplexes. It is proposed that RNA-DNA triplexes guide RNA-associated regulatory proteins to specific genomic locations, influencing transcription and epigenetic decision making. Although triplex formation initially was considered solely an in vitro event, recent progress in computational, biochemi...
Source: Trends in Biochemical Sciences - April 6, 2024 Category: Biochemistry Authors: Matthias S Leisegang Timothy Warwick Julia St ötzel Ralf P Brandes Source Type: research

RNA-DNA triplexes: molecular mechanisms and functional relevance
Trends Biochem Sci. 2024 Apr 5:S0968-0004(24)00075-6. doi: 10.1016/j.tibs.2024.03.009. Online ahead of print.ABSTRACTInteractions of RNA with DNA are principles of gene expression control that have recently gained considerable attention. Among RNA-DNA interactions are R-loops and RNA-DNA hybrid G-quadruplexes, as well as RNA-DNA triplexes. It is proposed that RNA-DNA triplexes guide RNA-associated regulatory proteins to specific genomic locations, influencing transcription and epigenetic decision making. Although triplex formation initially was considered solely an in vitro event, recent progress in computational, biochemi...
Source: Trends in Biochemical Sciences - April 6, 2024 Category: Biochemistry Authors: Matthias S Leisegang Timothy Warwick Julia St ötzel Ralf P Brandes Source Type: research

RNA-DNA triplexes: molecular mechanisms and functional relevance
Trends Biochem Sci. 2024 Apr 5:S0968-0004(24)00075-6. doi: 10.1016/j.tibs.2024.03.009. Online ahead of print.ABSTRACTInteractions of RNA with DNA are principles of gene expression control that have recently gained considerable attention. Among RNA-DNA interactions are R-loops and RNA-DNA hybrid G-quadruplexes, as well as RNA-DNA triplexes. It is proposed that RNA-DNA triplexes guide RNA-associated regulatory proteins to specific genomic locations, influencing transcription and epigenetic decision making. Although triplex formation initially was considered solely an in vitro event, recent progress in computational, biochemi...
Source: Trends in Biochemical Sciences - April 6, 2024 Category: Biochemistry Authors: Matthias S Leisegang Timothy Warwick Julia St ötzel Ralf P Brandes Source Type: research

ULK/Atg1: phasing in and out of autophagy
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00065-3. doi: 10.1016/j.tibs.2024.03.004. Online ahead of print.ABSTRACTAutophagy - a highly regulated intracellular degradation process - is pivotal in maintaining cellular homeostasis. Liquid-liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) fa...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Bo Wang Gautam Pareek Mondira Kundu Source Type: research

Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00071-9. doi: 10.1016/j.tibs.2024.03.005. Online ahead of print.ABSTRACTIn mitochondria, the oxidation of nutrients is coupled to ATP synthesis by the generation of a protonmotive force across the mitochondrial inner membrane. In mammalian brown adipose tissue (BAT), uncoupling protein 1 (UCP1, SLC25A7), a member of the SLC25 mitochondrial carrier family, dissipates the protonmotive force by facilitating the return of protons to the mitochondrial matrix. This process short-circuits the mitochondrion, generating heat for non-shivering thermogenesis. Recent cryo-electron microscop...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Scott A Jones Jonathan J Ruprecht Paul G Crichton Edmund R S Kunji Source Type: research

ULK/Atg1: phasing in and out of autophagy
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00065-3. doi: 10.1016/j.tibs.2024.03.004. Online ahead of print.ABSTRACTAutophagy - a highly regulated intracellular degradation process - is pivotal in maintaining cellular homeostasis. Liquid-liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) fa...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Bo Wang Gautam Pareek Mondira Kundu Source Type: research

Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00071-9. doi: 10.1016/j.tibs.2024.03.005. Online ahead of print.ABSTRACTIn mitochondria, the oxidation of nutrients is coupled to ATP synthesis by the generation of a protonmotive force across the mitochondrial inner membrane. In mammalian brown adipose tissue (BAT), uncoupling protein 1 (UCP1, SLC25A7), a member of the SLC25 mitochondrial carrier family, dissipates the protonmotive force by facilitating the return of protons to the mitochondrial matrix. This process short-circuits the mitochondrion, generating heat for non-shivering thermogenesis. Recent cryo-electron microscop...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Scott A Jones Jonathan J Ruprecht Paul G Crichton Edmund R S Kunji Source Type: research

ULK/Atg1: phasing in and out of autophagy
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00065-3. doi: 10.1016/j.tibs.2024.03.004. Online ahead of print.ABSTRACTAutophagy - a highly regulated intracellular degradation process - is pivotal in maintaining cellular homeostasis. Liquid-liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) fa...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Bo Wang Gautam Pareek Mondira Kundu Source Type: research