PDBsum entry 1csc

Oxo-acid-lyase

PDB id: 1csc

Contents

Protein chain

429 a.a. *

Ligands

CMC

LMR

Waters ×101

* Residue conservation analysis

PDB id:

1csc

Name:

Oxo-acid-lyase

Title:

Structure of ternary complexes of citrate synthase with d-and l- malate: mechanistic implications

Structure:

Citrate synthase. Chain: a. Engineered: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031

Biol. unit:

Dimer (from PQS)

Resolution:

1.70Å R-factor: 0.188

Authors:

M.Karpusas,D.Holland,S.J.Remington

Key ref:

M.Karpusas et al. (1991). 1.9-A structures of ternary complexes of citrate synthase with D- and L-malate: mechanistic implications. Biochemistry, 30, 6024-6031. PubMed id: 2043640 DOI: 10.1021/bi00238a028

Date:

07-May-90 Release date: 15-Apr-91

Protein chain

P23007  (CISY_CHICK) -  Citrate synthase, mitochondrial from Gallus gallus

Seq: 433 a.a.

Struc: 429 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.3.1 - citrate (Si)-synthase.
• Pathway: Citric acid cycle
• Reaction: oxaloacetate + acetyl-CoA + H2O = citrate + CoA + H⁺

oxaloacetate (Bound ligand (Het Group name = CMC) matches with 94.34% similarity) + acetyl-CoA + H2O (Bound ligand (Het Group name = LMR) corresponds exactly) = citrate + CoA + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi00238a028

Biochemistry 30:6024-6031 (1991)

PubMed id: 2043640

1.9-A structures of ternary complexes of citrate synthase with D- and L-malate: mechanistic implications.

M.Karpusas, D.Holland, S.J.Remington.

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).