1csc: Difference between revisions
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[[Image:1csc.gif|left|200px]]<br /><applet load="1csc" size=" | [[Image:1csc.gif|left|200px]]<br /><applet load="1csc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1csc, resolution 1.7Å" /> | caption="1csc, resolution 1.7Å" /> | ||
'''STRUCTURE OF TERNARY COMPLEXES OF CITRATE SYNTHASE WITH D-AND L-MALATE: MECHANISTIC IMPLICATIONS'''<br /> | '''STRUCTURE OF TERNARY COMPLEXES OF CITRATE SYNTHASE WITH D-AND L-MALATE: MECHANISTIC IMPLICATIONS'''<br /> | ||
==Overview== | ==Overview== | ||
The structures of four isomorphous crystals of ternary complexes of | 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 Structure== | ==About this Structure== | ||
1CSC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with MAL and CMC as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Citrate_(Si)-synthase Citrate (Si)-synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.1 2.3.3.1] Full crystallographic information is available from [http:// | 1CSC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with <scene name='pdbligand=MAL:'>MAL</scene> and <scene name='pdbligand=CMC:'>CMC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Citrate_(Si)-synthase Citrate (Si)-synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.1 2.3.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CSC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Holland, D.]] | [[Category: Holland, D.]] | ||
[[Category: Karpusas, M.]] | [[Category: Karpusas, M.]] | ||
[[Category: Remington, S | [[Category: Remington, S J.]] | ||
[[Category: CMC]] | [[Category: CMC]] | ||
[[Category: MAL]] | [[Category: MAL]] | ||
[[Category: oxo-acid-lyase]] | [[Category: oxo-acid-lyase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:09:17 2008'' | ||
Revision as of 13:09, 21 February 2008
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STRUCTURE OF TERNARY COMPLEXES OF CITRATE SYNTHASE WITH D-AND L-MALATE: MECHANISTIC IMPLICATIONS
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 and 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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