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Full-Text Articles in Medicine and Health Sciences
Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou
Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …
Wild-Type And Mutant Sod1 Share An Aberrant Conformation And A Common Pathogenic Pathway In Als., Daryl A Bosco, Gerardo Morfini, N Murat Karabacak, Yuyu Song, Francois Gros-Louis, Piera Pasinelli, Holly Goolsby, Benjamin A Fontaine, Nathan Lemay, Diane Mckenna-Yasek, Matthew P Frosch, Jeffrey N Agar, Jean-Pierre Julien, Scott T Brady, Robert H Brown
Wild-Type And Mutant Sod1 Share An Aberrant Conformation And A Common Pathogenic Pathway In Als., Daryl A Bosco, Gerardo Morfini, N Murat Karabacak, Yuyu Song, Francois Gros-Louis, Piera Pasinelli, Holly Goolsby, Benjamin A Fontaine, Nathan Lemay, Diane Mckenna-Yasek, Matthew P Frosch, Jeffrey N Agar, Jean-Pierre Julien, Scott T Brady, Robert H Brown
Farber Institute for Neuroscience Faculty Papers
Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal …
S100a1: A Multifaceted Therapeutic Target In Cardiovascular Disease., David Rohde, Julia Ritterhoff, Mirko Voelkers, Hugo A Katus, Thomas G Parker, Patrick Most
S100a1: A Multifaceted Therapeutic Target In Cardiovascular Disease., David Rohde, Julia Ritterhoff, Mirko Voelkers, Hugo A Katus, Thomas G Parker, Patrick Most
Department of Medicine Faculty Papers
Cardiovascular disease is the leading cause of death worldwide, showing a dramatically growing prevalence. It is still associated with a poor clinical prognosis, indicating insufficient long-term treatment success of currently available therapeutic strategies. Investigations of the pathomechanisms underlying cardiovascular disorders uncovered the Ca(2+) binding protein S100A1 as a critical regulator of both cardiac performance and vascular biology. In cardiomyocytes, S100A1 was found to interact with both the sarcoplasmic reticulum ATPase (SERCA2a) and the ryanodine receptor 2 (RyR2), resulting in substantially improved Ca(2+) handling and contractile performance. Additionally, S100A1 has been described to target the cardiac sarcomere and mitochondria, leading to …
Control Of Catalytic Cycle By A Pair Of Analogous Trna Modification Enzymes., Thomas Christian, Georges Lahoud, Cuiping Liu, Ya-Ming Hou
Control Of Catalytic Cycle By A Pair Of Analogous Trna Modification Enzymes., Thomas Christian, Georges Lahoud, Cuiping Liu, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Enzymes that use distinct active site structures to perform identical reactions are known as analogous enzymes. The isolation of analogous enzymes suggests the existence of multiple enzyme structural pathways that can catalyze the same chemical reaction. A fundamental question concerning analogous enzymes is whether their distinct active-site structures would confer the same or different kinetic constraints to the chemical reaction, particularly with respect to the control of enzyme turnover. Here, we address this question with the analogous enzymes of bacterial TrmD and its eukaryotic and archaeal counterpart Trm5. TrmD and Trm5 catalyze methyl transfer to synthesize the m1G37 base at …
Control Of Catalytic Cycle By A Pair Of Analogous Trna Modification Enzymes., Thomas Christian, Georges Lahoud, Cuiping Liu, Ya-Ming Hou
Control Of Catalytic Cycle By A Pair Of Analogous Trna Modification Enzymes., Thomas Christian, Georges Lahoud, Cuiping Liu, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Enzymes that use distinct active site structures to perform identical reactions are known as analogous enzymes. The isolation of analogous enzymes suggests the existence of multiple enzyme structural pathways that can catalyze the same chemical reaction. A fundamental question concerning analogous enzymes is whether their distinct active-site structures would confer the same or different kinetic constraints to the chemical reaction, particularly with respect to the control of enzyme turnover. Here, we address this question with the analogous enzymes of bacterial TrmD and its eukaryotic and archaeal counterpart Trm5. TrmD and Trm5 catalyze methyl transfer to synthesize the m1G37 base at …
Ribosome Recycling Step In Yeast Cytoplasmic Protein Synthesis Is Catalyzed By Eef3 And Atp., Shinya Kurata, Klaus H Nielsen, Sarah F Mitchell, Jon R Lorsch, Akira Kaji, Hideko Kaji
Ribosome Recycling Step In Yeast Cytoplasmic Protein Synthesis Is Catalyzed By Eef3 And Atp., Shinya Kurata, Klaus H Nielsen, Sarah F Mitchell, Jon R Lorsch, Akira Kaji, Hideko Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
After each round of protein biosynthesis, the posttermination complex (PoTC) consisting of a ribosome, mRNA, and tRNA must be disassembled into its components for a new round of translation. Here, we show that a Saccharomyces cerevisiae model PoTC was disassembled by ATP and eukaryotic elongation factor 3 (eEF3). GTP or ITP functioned with less efficiency and adenosine 5gamma'-(beta,gamma-imido)triphosphate did not function at all. The k(cat) of eEF3 was 1.12 min(-1), which is comparable to that of the in vitro initiation step. The disassembly reaction was inhibited by aminoglycosides and cycloheximide. The subunits formed from the yeast model PoTC remained separated …