Reduced pH induces an inactive non-native conformation of the monomeric bothropstoxin-I (Lys49-PLA(2))

Author(s)

de Oliveira, Arthur H. C. ^[1] ; Ferreira, Tatiana L. ^[2] ; Ward, Richard J. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Pret, Dept Quim, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Verdartis Desenvolvimento Biotecnol Ltda ME, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Toxicon; v. 54, n. 3, p. 373-378, SEP 1 2009.
• Web of Science Citations: 4

Abstract

Bothropstoxin-I (BthTx-I), a Lys49-PLA(2) from Bothrops jararacussu venom, permeabilizes membranes by a non-hydrolytic Ca(2+)-independent mechanism. The BthTx-I showed activity against liposomes including 10% and 50% negatively charged lipids at pH 7.0, but not at pH 5.0. Nevertheless, ultracentrifugation and FRET demonstrated that at pH 5.0 the BthTx-I is bound to 50% negatively charged membranes. ANS binding identified a non-native monomeric conformation at pH 5.0, suggesting that tertiary structure alterations result in activity loss of the BthTx-I at low pH. (C) 2009 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 07/06755-2 - Structural and functional characterization of proteins envolved in the virulence of the protozoan parasite Leishmania major
• Grantee: Arthur Henrique Cavalcante de Oliveira
• Support Opportunities: Regular Research Grants