Poster 222 - Structural and phylogenetic analysis of snake venom bradykinin-potentiating peptides

Poster 222. Congresso da Sociedade Brasileira de Toxinologia, 8., Symposium of the Pan American Section of the International Society on Toxinology, 8., 2004, Angra dos Reis, Brasil. Abstracts... J. Venom. Anim. Toxins incl.Trop. Dis., 2004, 10, 3, p.581.

Structural And Phylogenetic Analysis Of Snake Venom Bradykinin-Potentiating Peptides

1 Departamento de Farmacologia, FCM, Universidade Estadual de Campinas (UNICAMP), Campinas, SP; 2 Departamento de Histologia e Embriologia, Programa de Biologia Celular, ICB, Universidade de São Paulo (USP), São Paulo, SP, Brazil.

Snake venom bradykinin-potentiating peptides (BPPs) inhibit angiotensin-converting enzyme (ACE) and potentiate hypotensive responses to bradykinin. In this work, we compared the structures of BPPs and examined the phylogenetic relationships among them. Forty-nine BPP sequences from venoms of the genera Agkistrodon, Bothrops, Crotalus and Trimeresurus were compiled from literature reports. Multiple and pairwise sequence alignments were done with Clustal X. Rooted and unrooted phylogenetic trees were constructed using TreeView. The BPP sequences were also used to search the ProSite and Protein Data Bank databases for putative endogenous protein sources. Primary structure analysis showed that BPPs contained 3-13 amino peptides with an N-terminal pGlu and in most cases a C-terminal tripeptide (Ile/Val-Pro/Ser-Pro). Sequence alignments showed the greatest homologies at positions 2, 4, 8, 10, 12, 16, 17 and 18 (positions numbered according to the least-gap alignment). Unrooted trees showed no well-defined groups, with peptides from several genera often occurring in the same branch. However, rooted dendrograms revealed 3-4 major branches, each with peptides from a variety of species and genera. In all analyses, two peptides (QSKPGRSPPISP from Trimeresurusflavoviridis and QFKPGRSPPISP from Trimeresurusgramineus) consistently segregated from other BPPs. A database search identified partial sequence homologies between five BPP (all from Bothropsspp.) and other proteins; two B. jararaca peptides (ENWPHPQIPP and ENWPRPQIPP) showed nearly complete matches with conserved RWD domains. These results indicate that although BPPs share similar structural homologies there are no clear phylogenetic relationships between them. BPPs also share little homology with other known proteins, a finding that agrees with these peptides being specific gene products.