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The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase

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Open access
Authors
Mancera, Ricardo
Carrington, B.
Date
2005
Type
Journal Article

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Mancera, Ricardo L. and Carrington, Benjamin J. 2005. The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase. Journal of Molecular Structure: THEOCHEM. 755 (91-30): 151-159.
Source Title
Journal of Molecular Structure: THEOCHEM
DOI
Faculty
Division of Health Sciences
School of Pharmacy
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NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Molecular Structure: THEOCHEM. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Molecular Structure: THEOCHEM, Volume 755, Issues 1–3, 30 November 2005, Pages 151–159, http://dx.doi.org/10.1016/j.theochem.2005.08.014

Copyright 2006 © Elsevier B.V.

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Abstract

We have performed molecular modelling studies of the binding to maize phosphoenolpyruvate carboxylase (PEPC) of phosphoenolpyruvate (PEP) and a number of representative competitive inhibitors. We predict that all these compounds share a common binding mode and that the differences in inhibitory activity of the various inhibitors arise mainly from either increased hydrophobic interactions of cis substituents or small but significant changes in their binding mode arising from steric clashes of trans substituents with the active site. We have also performed molecular modelling studies of glucose-6-phosphate (G6P) and a number of other allosteric activators in their putative allosteric binding site in this enzyme. We predict that these molecules share the same binding mode for their phosphate moiety while some of them engage in a variety of hydrogen bonding interactions with residues from different subunits of the enzyme, and others establish hydrophobic and van der Waals interactions with other regions of the allosteric binding site.