Title |
Rational Engineering of Enzyme Allosteric Regulation through Sequence Evolution Analysis
|
---|---|
Published in |
PLoS Computational Biology, July 2012
|
DOI | 10.1371/journal.pcbi.1002612 |
Pubmed ID | |
Authors |
Jae-Seong Yang, Sang Woo Seo, Sungho Jang, Gyoo Yeol Jung, Sanguk Kim |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 25% |
Japan | 1 | 25% |
Canada | 1 | 25% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 2 | 50% |
Members of the public | 1 | 25% |
Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 2% |
Korea, Republic of | 2 | 1% |
United Kingdom | 1 | <1% |
Canada | 1 | <1% |
Chile | 1 | <1% |
Russia | 1 | <1% |
Denmark | 1 | <1% |
Japan | 1 | <1% |
Spain | 1 | <1% |
Other | 0 | 0% |
Unknown | 157 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 52 | 31% |
Researcher | 25 | 15% |
Student > Master | 22 | 13% |
Student > Bachelor | 17 | 10% |
Professor > Associate Professor | 11 | 7% |
Other | 21 | 12% |
Unknown | 21 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 65 | 38% |
Biochemistry, Genetics and Molecular Biology | 35 | 21% |
Chemistry | 19 | 11% |
Chemical Engineering | 6 | 4% |
Engineering | 6 | 4% |
Other | 14 | 8% |
Unknown | 24 | 14% |