Crystal structure of the gephyrin-related molybdenum cofactor biosynthesis protein MogA from Escherichia coli.
Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway in archaea, eubacteria, and eukaryotes, including humans. Genetic deficiencies of enzymes involved in this biosynthetic pathway trigger an autosomal recessive disease with severe neurological symptoms, which usually leads to death in early childhood. The MogA protein exhibits affinity for molybdopterin, the organic component of Moco, and has been proposed to act as a molybdochelatase incorporating molybdenum into Moco. MogA is related to the protein gephyrin, which, in addition to its role in Moco biosynthesis, is also responsible for anchoring glycinergic receptors to the cytoskeleton at inhibitory synapses. The high resolution crystal structure of the Escherichia coli MogA protein has been determined, and it reveals a trimeric arrangement in which each monomer contains a central, mostly parallel beta-sheet surrounded by alpha-helices on either side. Based on structural and biochemical data, a putative active site was identified, including two residues that are essential for the catalytic mechanism.
Liu
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Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794-5215, USA.
Wuebbens
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Schindelin
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D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics*; D001665:Binding Sites; D003001:Cloning, Molecular; D003067:Coenzymes / Q000737:chemistry / Q000235:genetics; D017124:Conserved Sequence; D003461:Crystallography; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D008667:Metalloproteins / Q000378:metabolism*; D008958:Models, Molecular; D000090006:Molybdenum Cofactors; D016297:Mutagenesis, Site-Directed; D050901:Nitrate Reductase; D009565:Nitrate Reductases / Q000378:metabolism; D017510:Protein Folding; D011621:Pteridines / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D003067:Coenzymes; D029968:Escherichia coli Proteins; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D050901:Nitrate Reductase; D009565:Nitrate Reductases; D011621:Pteridines; C404104:Mog protein, E coli; C022261:molybdopterin