Rational Engineering of Enzyme Allosteric Regulation through Sequence Evolution Analysis
(A) Representative mapping of catalytic, allosteric, and surface residues on 3D structures, represented in red, cyan, and gray, respectively. Allosteric sites of enzymes are generally located away from catalytic sites. Conservation scores were calculated for each residue from homologous sequences collected from the UniProtKB/SwissProt database. To compare conservation scores among different proteins, we applied the percentile normalization method. Conservation scores range from 0 to 1. Highly conserved residues get larger conservation scores. (B) Distributions of conservation scores for catalytic, allosteric, and surface residues. Shown are the distributions of conservation scores of residues collected from 56 allosteric proteins. The annotation of each residue comes from hand-curated databases. (C) Distributions of average conservation scores of catalytic, allosteric, and surface residues per protein. (D) Distributions of enzyme classes in our dataset and in the entire ENZYME database. The statistical significance (P-value) was measured by the Mann-Whitney U test.