Metal toxicity and opportunistic binding of Pb(2+) in proteins.

ABSTRACT: Lead toxicity is associated with various human diseases. While Ca(2+) binding proteins such as calmodulin (CaM) are often reported to be molecular targets for Pb(2+)-binding and lead toxicity, the effect of Pb(2+) on the Ca(2+)/CaM regulated biological activities cannot be described by the primary mechanism of ionic displacement (e.g., ionic mimicry). The focus of this study was to investigate the mechanism of lead toxicity through binding differences between Ca(2+) and Pb(2+) for CaM, an essential intracellular trigger protein with two EF-Hand Ca(2+)-binding sites in each of its two domains that regulates many molecular targets via Ca(2+)-induced conformational change. Fluorescence changes in phenylalanine indicated that Pb(2+) binds with 8-fold higher affinity than Ca(2+) in the N-termin

SUBMITTER: Kirberger M 

PROVIDER: S-EPMC3947799 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature