Prediction of catalytic residues in enzymes based on known tertiary structure, stability profile, and sequence conservation.
The catalytic or functionally important residues of a protein are known to exist in evolutionarily constrained regions. However, the patterns of residue conservation alone are sometimes not very informative, depending on the homologous sequences available for a given query protein. Here, we present an integrated method to locate the catalytic residues in an enzyme from its sequence and structure. Mutations of functional residues usually decrease the activity, but concurrently often increase stability. Also, catalytic residues tend to occupy partially buried sites in holes or clefts on the molecular surface. After confirming these general tendencies by carrying out statistical analyses on 49 representative enzymes, these data together with amino acid conservation were evaluated. This novel method exhibited better sensitivity in the prediction accuracy than traditional methods that consider only the residue conservation. We applied it to some so-called "hypothetical" proteins, with known structures but undefined functions. The relationships among the catalytic, conserved, and destabilizing residues in enzymatic proteins are discussed.
Ota
Motonori
M
National Institute of Genetics, Yata, Mishima, 411-8540, Shizuoka, Japan. mota@gsic.titech.ac.jp
Kinoshita
Kengo
K
Nishikawa
Ken
K
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D004795:Enzyme Stability; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D004798:Enzymes