THE INTEGRASE FAMILY OF TYROSINE RECOMBINASES - EVOLUTION OF A CONSERVED ACTIVE-SITE DOMAIN

The integrases are a diverse family of tyrosine recombinases which rea rrange DNA duplexes by means of conservative site-specific recombinati on reactions. Members of this family, of which the well-studied lambda Int protein is the prototype, were previously found to share four str ongly conserved residues, including an active site tyrosine directly i nvolved in transesterification. However, few additional sequence simil arities were found in the original group of 27 proteins. We have now i dentified a total of 81 members of the integrase family deposited in t he databases, Alignment and comparisons of these sequences combined wi th an evolutionary analysis aided in identifying broader sequence simi larities and clarifying the possible functions of these conserved resi dues, This analysis showed that members of the family aggregate into s ubfamilies which are consistent with their biological roles; these sub families have significant levels of sequence similarity beyond the fou r residues previously identified. It was also possible to map the loca tion 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 b etween the mechanisms of different subfamilies of integrases.