Fungicide methyl thiophanate binding at sub-domain IIA of human serum albumin triggers conformational change and protein damage

Fluorescence quenching data on interaction of a fungicide methyl thiophanate (MT) with human serum albumin (HSA) elucidated a primary binding site at sub-domain IIA. Stern-Volmer algorithm and double log plot revealed the binding affinity (K-a) and capacity (n) of HSA as 1.65 x 10(4) M-1 and 1.0 (r(2)=0.99), respectively. Cyclic voltammetric and circular dichroism (CD) studies reaffirmed MT-HSA binding and demonstrated reduction in alpha-helical content of HSA. Substantial release of the carbonyl and acid-soluble amino groups from MT treated HSA suggested protein damage. The plausible mechanism of methyl (+CH3) group transfer from MT to side chain NH group of tryptophan and HSA degradation elucidates the toxicological and clinical implications of this fungicide. (C) 2010 Elsevier B.V. All rights reserved.