1pjt
From Proteopedia
The structure of the Ser128Ala point-mutant variant of CysG, the multifunctional methyltransferase/dehydrogenase/ferrochelatase for siroheme synthesis
Structural highlights
FunctionCYSG_SALTY Multifunctional enzyme that catalyzes the SAM-dependent methylations of uroporphyrinogen III at position C-2 and C-7 to form precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it catalyzes the ferrochelation of sirohydrochlorin to yield siroheme.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSulfur 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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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