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The co-crystal structure of CysG, the multifunctional methyltransferase/dehydrogenase/ferrochelatase for siroheme synthesis, in complex with it NAD cofactor
Overview
Sulfur metabolism depends on the iron-containing porphinoid siroheme. In, Salmonella enterica, the S-adenosyl-L-methionine (SAM)-dependent, bismethyltransferase, dehydrogenase and ferrochelatase, CysG, synthesizes, siroheme from uroporphyrinogen III (uro'gen III). The reactions mediated, by CysG encompass two branchpoint intermediates in tetrapyrrole, biosynthesis, diverting flux first from protoporphyrin IX biosynthesis and, then from cobalamin (vitamin B(12)) biosynthesis. We determined the first, structure of this multifunctional siroheme synthase by X-ray, crystallography. CysG is a homodimeric gene fusion product containing two, structurally independent modules: a bismethyltransferase and a, dual-function dehydrogenase-chelatase. The methyltransferase active site, is a deep groove with a hydrophobic patch surrounded by hydrogen bond, donors. This asymmetric arrangement of amino acids may be important in, directing substrate binding. Notably, our structure shows that CysG is a, phosphoprotein. From mutational analysis of the post-translationally, modified serine, we suggest a conserved role for phosphorylation in, inhibiting dehydrogenase activity and modulating metabolic flux between, siroheme and cobalamin pathways.
About this Structure
1PJS is a Single protein structure of sequence from Salmonella typhimurium with PO4, SAH, NAD and PGE as ligands. Full crystallographic information is available from OCA.
Reference
CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis., Stroupe ME, Leech HK, Daniels DS, Warren MJ, Getzoff ED, Nat Struct Biol. 2003 Dec;10(12):1064-73. Epub 2003 Nov 2. PMID:14595395
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