The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase

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 act...

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Main Authors: Mancera, Ricardo, Carrington, B.
Format: Journal Article
Published: Elsevier 2005
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/8995
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author Mancera, Ricardo
Carrington, B.
author_facet Mancera, Ricardo
Carrington, B.
author_sort Mancera, Ricardo
building Curtin Institutional Repository
collection Online Access
description 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.
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institution Curtin University Malaysia
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publishDate 2005
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spelling curtin-20.500.11937-89952019-02-19T05:35:29Z The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase Mancera, Ricardo Carrington, B. Phosphoenolpyruvate Carboxylase Inhibitors Activators Docking 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. 2005 Journal Article http://hdl.handle.net/20.500.11937/8995 10.1016/j.theochem.2005.08.014 Elsevier fulltext
spellingShingle Phosphoenolpyruvate Carboxylase
Inhibitors
Activators
Docking
Mancera, Ricardo
Carrington, B.
The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
title The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
title_full The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
title_fullStr The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
title_full_unstemmed The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
title_short The molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
title_sort molecular binding interactions of inhibitors and activators of phosphoenolpyruvate carboxylase
topic Phosphoenolpyruvate Carboxylase
Inhibitors
Activators
Docking
url http://hdl.handle.net/20.500.11937/8995