1csc
STRUCTURE OF TERNARY COMPLEXES OF CITRATE SYNTHASE WITH D-AND L-MALATE: MECHANISTIC IMPLICATIONS
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OverviewOverview
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).
About this StructureAbout this Structure
1CSC is a Single protein structure of sequence from Gallus gallus with MAL and CMC as ligands. Active as Citrate (Si)-synthase, with EC number 2.3.3.1 Full crystallographic information is available from OCA.
ReferenceReference
1.9-A structures of ternary complexes of citrate synthase with D- and L-malate: mechanistic implications., Karpusas M, Holland D, Remington SJ, Biochemistry. 1991 Jun 18;30(24):6024-31. PMID:2043640
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