"Lethal Synthesis" of Fluorocitrate by Citrate Synthase Explained through QM/MM Modeling

A classic example of enzyme stereospecificity is the title reaction involving the enantioselective conversion of fluoroacetyl‐CoA. High‐level modeling of the enzyme reaction shows that preferential formation of an E‐enolate explains the experimentally observed specificity. The results indicate that...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2011-10, Vol.50 (44), p.10349-10351
Main Authors: van der Kamp, Marc W., McGeagh, John D., Mulholland, Adrian J.
Format: Article
Language:English
Subjects:
ab initio calculations
Acetyl Coenzyme A - chemistry
Citrate (si)-Synthase - chemistry
citrate synthase
Citrates - biosynthesis
computational enzymology
enantioselectivity
enzyme catalysis
Quantum Theory
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Summary:A classic example of enzyme stereospecificity is the title reaction involving the enantioselective conversion of fluoroacetyl‐CoA. High‐level modeling of the enzyme reaction shows that preferential formation of an E‐enolate explains the experimentally observed specificity. The results indicate that selectivity is primarily a result of the inherent energy difference between the E‐ and Z‐enolates of fluoroacetyl‐CoA.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201103260