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Cited 37 time in webofscience Cited 40 time in scopus
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Rational Engineering of Enzyme Allosteric Regulation through Sequence Evolution Analysis

Title
Rational Engineering of Enzyme Allosteric Regulation through Sequence Evolution Analysis
Authors
Yang, JSSeo, SWJang, SJung, GYKim, S
POSTECH Authors
Jung, GYKim, S
Date Issued
Jul-2012
Publisher
Public Library of Science
Abstract
Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D) structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligand-binding sites. We found that allosteric sites are evolutionarily variable and comprised of more hydrophobic residues than catalytic sites. We applied our findings to design mutations in selected target residues that deregulate the allosteric activity of fructose-1,6-bisphosphatase (FBPase). Specifically, charged amino acids at less conserved positions were substituted with hydrophobic or neutral amino acids with similar sizes. The engineered proteins successfully diminished the allosteric inhibition of E. coli FBPase without affecting its catalytic efficiency. We expect that our method will aid the rational design of enzyme allosteric regulation strategies and facilitate the control of metabolic flux.
URI
http://oasis.postech.ac.kr/handle/2014.oak/16401
DOI
10.1371/JOURNAL.PCBI.1002612
ISSN
1553-7358
Article Type
Article
Citation
PLOS COMPUTATIONAL BIOLOGY, vol. 8, no. 7, page. E1002612 - E1002612, 2012-07
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 KIM, SANGUK
Dept of Life Sciences
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