title: The integrase family of tyrosine recombinases: evolution of a conserved active site domain.
abstract: The integrases are a diverse family of tyrosine recombinases which rearrange DNA duplexes by means of conservative site-specific recombination reactions. Members of this family, of which the well-studied lambda Int protein is the prototype, were previously found to share four strongly conserved residues, including an active site tyrosine directly involved in transesterification. However, few additional sequence similarities were found in the original group of 27 proteins. We have now identified a total of 81 members of the integrase family deposited in the databases. Alignment and comparisons of these sequences combined with an evolutionary analysis aided in identifying broader sequence similarities and clarifying the possible functions of these conserved residues. This analysis showed that members of the family aggregate into subfamilies which are consistent with their biological roles; these subfamilies have significant levels of sequence similarity beyond the four residues previously identified. It was also possible to map the location of conserved residues onto the available crystal structures; most of the conserved residues cluster in the predicted active site cleft. In addition, these results offer clues into an apparent discrepancy between the mechanisms of different subfamilies of integrases.
authors.affiliation: Laboratory of Molecular Biology, NIDDK, National Institutes of Health, 5 Center Drive MSC0560, Bethesda, MD 20782, USA. domespo@helix.nih.gov
authors.forename: D
authors.initials: D
authors.lastname: Esposito
authors.forename: J J
authors.initials: JJ
authors.lastname: Scocca
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D019426:Integrases / Q000235:genetics*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017421:Sequence Analysis
chemical_list: D019426:Integrases