1PJS

The co-crystal structure of CysG, the multifunctional methyltransferase/dehydrogenase/ferrochelatase for siroheme synthesis, in complex with it NAD cofactor

1PJS の概要

• エントリーDOI: 10.2210/pdb1pjs/pdb
• 関連するPDBエントリー: 1PJQ 1PJT
• 分子名称: Siroheme synthase, S-ADENOSYL-L-HOMOCYSTEINE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: rossmann fold, nucleotide binding motif, sah, sam, nad, phosphoserine, transferase-oxidoreductase-lyase complex, transferase/oxidoreductase/lyase
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 103063.94

構造登録者

Stroupe, M.E.,Leech, H.K.,Daniels, D.S.,Warren, M.J.,Getzoff, E.D. (登録日: 2003-06-03, 公開日: 2003-12-02, 最終更新日: 2024-11-06)

主引用文献

Stroupe, M.E.,Leech, H.K.,Daniels, D.S.,Warren, M.J.,Getzoff, E.D.
CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis.
Nat.Struct.Biol., 10:1064-1073, 2003

PubMed Abstract: 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.

PubMed: 14595395
DOI: 10.1038/nsb1007

実験手法

X-RAY DIFFRACTION (2.4 Å)