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Computational simulation of ligand docking to L-type pyruvate kinase subunit

Paper ID Volume ID Publish Year Pages File Format Full-Text
15140 1381 2014 5 PDF Available
Title
Computational simulation of ligand docking to L-type pyruvate kinase subunit
Abstract

•Computational docking revealed binding sites of L-type pyruvate kinase N-domain in domains A and C of the protein.•Peptide RRASVA and its phosphor-analogue were used to model the regulatory N-domain.•Phosphorylation shifted the peptide binding from domain A to domain C.•Shift of N-domain interaction site may explain switching on L-PK cooperativity by phosphorylation.

Computational blind docking approach was used for mapping of possible binding sites in L-type pyruvate kinase subunit for peptides, RRASVA and the phosphorylated derivative RRAS(Pi)VA, which model the phosphorylatable N-terminal regulatory domain of the enzyme. In parallel, the same docking analysis was done for both substrates of this enzyme, phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP), and for docking of fructose 1,6-bisphosphate (FBP), which is the allosteric activator of the enzyme. The binding properties of the entire surface of the protein were scanned and several possible binding sites were identified in domains A and C of the protein, while domain B revealed no docking sites for peptides or for substrates or the allosteric regulator. It was found that the docking sites of different ligands were partially overlapping, pointing to the possibility that some regulatory effects, observed in the case of L-type pyruvate kinase, may be caused by the competition of different ligands for the same binding sites.

Graphical abstractPossible docking sites for N-terminal regulatory domain of L-type pyruvate kinase in domains A and C of the protein.Figure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
L-type pyruvate kinase; N-terminal domain docking in protein; Regulatory phosphorylation; Putative N-terminal docking sites; Substrate affinity regulation; Switching in cooperativity
First Page Preview
Computational simulation of ligand docking to L-type pyruvate kinase subunit
Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 48, February 2014, Pages 40–44
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering