A computational analysis of substrate binding strength by phosphorylase kinase and protein kinase A

Brinkworth, R. I., Horne, J. and Kobe, B. (2002) A computational analysis of substrate binding strength by phosphorylase kinase and protein kinase A. Journal of Molecular Recognition, 15 2: 104-111. doi:10.1002/jmr.563


Author Brinkworth, R. I.
Horne, J.
Kobe, B.
Title A computational analysis of substrate binding strength by phosphorylase kinase and protein kinase A
Journal name Journal of Molecular Recognition   Check publisher's open access policy
ISSN 0952-3499
1099-1352
Publication date 2002-03
Sub-type Article (original research)
DOI 10.1002/jmr.563
Volume 15
Issue 2
Start page 104
End page 111
Total pages 10
Place of publication Sussex
Publisher John Wiley & Sons Ltd
Language eng
Abstract Protein kinases exhibit various degrees of substrate specificity. The large number of different protein kinases in the eukaryotic proteomes makes it impractical to determine the specificity of each enzyme experimentally. To test if it were possible to discriminate potential substrates from non-substrates by simple computational techniques, we analysed the binding enthalpies of modelled enzyme-substrate complexes and attempted to correlate it with experimental enzyme kinetics measurements. The crystal structures of phosphorylase kinase and cAMP-dependent protein kinase were used to generate models of the enzyme with a series of known peptide substrates and non-substrates, and the approximate enthalpy of binding assessed following energy minimization. We show that the computed enthalpies do not correlate closely with kinetic measurements, but the method can distinguish good substrates from weak substrates and non-substrates. Copyright (C) 2002 John Wiley Sons, Ltd.
Keyword Biochemistry & Molecular Biology
Biophysics
Molecular Modelling
Phosphorylase Kinase
Protein Kinase
Protein Kinase A/camp-dependent Protein
Kinase
Substrate Specificity
Three-dimensional Structure
Catalytic Subunit
Crystal-structure
Inhibitor
Specificity
Recognition
Complex
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 13 Aug 2007, 12:55:35 EST