Analysis and prediction of the location of catalytic residues in enzymes |
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Authors: | Zvelebil Marketa JJM; Sternberg Michael JE |
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Affiliation: | Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College Malet Street, London WC1E 7HX, UK |
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Abstract: | The catalytic residues of an enzyme are defined as the aminoacids directly involved in chemical catalysis. They mainly actas a general acidbase, electrophilic or nucleophiliccatalyst or they polarize and stabilize the transition state.An analysis of the structural features of 36 catalytic residuesin 17 enzymes of known structure and with defined mechanismis reported. Residues that bind metal ions (Zn2 and Cu2 ) areconsidered separately. The features examined are: residue type,location in secondary structure, separation between the residues,accessibility to solvent, intra-protein electrostatic interactions,mobility as evaluated from crystallographic temperature factors,polarity of the environment and the sequence conservation betweenhomologous enzymes of residues that were sequentially or spatiallyclose to the catalytic residue. In general the environment ofcatalytic residues is similar to that of polar side chains thathave low accessibility to solvent. Two algorithms have beendeveloped to identify probable catalytic residues. Scanningan alignment of homologous enzyme sequences for peaks of sequenceconservation identifies 13 out of the 16 catalytic residueswith 50 residues overpredicted. When the conservation of thespatially close residues is used instead, a different set of13 residues are identified with 47 residues overpredicted. Acombination of the two algorithms identifies 11 residues with36 residues overpredicted. |
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Keywords: | catalytic residues/ metal-binding residues/ conservation/ prediction |
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