We studied the evolutionary relationships between gamma-carbonic anhydrase (gamma-CA) and a very diverse group of proteins that share the sequence motif characteristic of the left-handed parallel beta-helix (LbetaH) fold. This sequence motif is characterized by the imperfect tandem repetition of short hexapeptide units, which makes it difficult to obtain a reliable alignment based on sequence information alone. To solve this problem, we used a structural alignment of three members of the group with known crystallographic structures as a seed to obtain a reliable sequence alignment. Then, we applied protein maximum-parsimony and maximum-likelihood phylogenetic inference methods to this alignment. We found that gamma-CA belongs to a diverse superfamily of proteins that share the LbetaH domain. This superfamily is composed mainly of acyltransferases. The most remarkable feature of the phylogenetic tree obtained is that its main branches group together functionally related proteins, so that the coarse topology can be rather easily explained in terms of functional diversification. Regarding the main branch of the tree containing gamma-CA, we found that, in addition to the group of its closest relatives that had already been studied, gamma-CA is closely related to the tetrahydrodipicolinate N-succinyltransferases.
Copyright 2000 Academic Press.