1CSC

Structure of ternary complexes of citrate synthase with D-and L-malate: Mechanistic implications

1CSC の概要

• エントリーDOI: 10.2210/pdb1csc/pdb
• 分子名称: CITRATE SYNTHASE, CARBOXYMETHYL COENZYME *A, (2S)-2-hydroxybutanedioic acid, ... (4 entities in total)
• 機能のキーワード: oxo-acid-lyase
• 由来する生物種: Gallus gallus (chicken)
• 細胞内の位置: Mitochondrion matrix: P23007
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48281.83

構造登録者

Karpusas, M.,Holland, D.,Remington, S.J. (登録日: 1990-05-07, 公開日: 1991-04-15, 最終更新日: 2024-02-07)

主引用文献

Karpusas, M.,Holland, D.,Remington, S.J.
1.9-A structures of ternary complexes of citrate synthase with D- and L-malate: mechanistic implications.
Biochemistry, 30:6024-6031, 1991

PubMed Abstract: The structures of four isomorphous crystals of ternary complexes of chicken heart citrate synthase with D- or L-malate and acetyl coenzyme A or carboxymethyl coenzyme A have been determined by X-ray crystallography and fully refined at 1.9-A resolution. The structures show that both L-malate and D-malate bind in a very similar way in the presence of acetylCoA and that the enzyme conformation is "closed". Hydrogen bond geometry is suggested to account for the difference in binding constants of the two stereoisomers. The structures suggest that steric hindrance can account for the observation that proton exchange of acetyl coenzyme A with solvent is catalyzed by citrate synthase in the presence of L-malate but not D-malate. The ternary complexes with malate reveal the mode of binding of the substrate acetylCoA in the ground state. The carbonyl oxygen of the acetyl group is hydrogen bonded to a water molecule and to histidine 274, allowing unambiguous identification of the orientation of this group. The structures support the hypothesis that carboxymethyl coenzyme A is a transition-state analogue for the enolization step of the reaction (Bayer et al., 1981) and additionally support proposed mechanisms for the condensation reaction (Karpusas et al., 1990; Alter et al., 1990).

PubMed: 2043640
DOI: 10.1021/bi00238a028

実験手法

X-RAY DIFFRACTION (1.7 Å)