Reduced pH induces an inactive non-native conformation of the monomeric bothropstoxin-I (Lys49-PLA2)

被引：11

作者：

de Oliveira, Arthur H. C. ^{[1
]}

Ferreira, Tatiana L. ^{[2
]}

Ward, Richard J. ^{[1
]}

机构：

[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

来源：

TOXICON | 2009年 / 54卷 / 03期

基金：

巴西圣保罗研究基金会;

关键词：

Phospholipase A(2); Membrane permeabilization; Molten globule; LYSINE 49-PHOSPHOLIPASE A(2); MEMBRANE-DAMAGING ACTIVITY; LYS49 PHOSPHOLIPASE A(2); INDUCED DISSOCIATION; TRANSTHYRETIN; JARARACUSSU; MUTAGENESIS; RESIDUES; BINDING;

D O I：

10.1016/j.toxicon.2009.04.022

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Bothropstoxin-I (BthTx-I), a Lys49-PLA(2) from Bothrops jararacussu venom, permeabilizes membranes by a non-hydrolytic Ca2+-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.

引用

页码：373 / 378

页数：6

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