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DISSOCIATION OF ARSENITE-PEPTIDE COMPLEXES: TRIPHASIC NATURE, RATE CONSTANTS, HALF LIVES AND BIOLOGICAL IMPORTANCE
Citation:
KITCHIN, K. T. AND K. WALLACE. DISSOCIATION OF ARSENITE-PEPTIDE COMPLEXES: TRIPHASIC NATURE, RATE CONSTANTS, HALF LIVES AND BIOLOGICAL IMPORTANCE. JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 20(1):48-56, (2006).
Impact/Purpose:
To determine the number and the dissociation rate constants of different complexes formed from arsenite and two peptides, which can alter their structure and function and contribute to adverse health outcomes such as toxicity and carcinogenicity.
Description:
We determined the number and the dissociation rate constants of different complexes formed from arsenite and two peptides containing either one (RV AVGNDYASGYHYGV for peptide 20) or three cysteines (LE AWQGK VEGTEHLYSMK K for peptide 10) via radioactive 73As labeled arsenite and vacuum filtration methodology. Nonlinear regression analysis of the dissociation of both arsenite-peptide complexes showed that triphasic fits gave excellent r2 values (0.9859 for peptides 20 and 0.9890 for peptide 10). The first phase of arsenite-peptide dissociation had the largest span (decrease in binding) and the rate was too fast to be measured using vacuum filtration methods. The dissociation rate constants of arsenite-peptide complexes for the second phase were 0.35 and 0.54 min-1 and for the third phase were 0.0071 and 0.0045 min-1 for peptides 20 and 10, respectively. For peptide 20 the three spans of triphasic decay were 85%, 9% and 7% of the total binding of 16.1 nmol/mg protein. For peptide 10 which can bind in both an intermolecular and intramolecular manner, the three spans of triphasic decay were 59%, 16% and 25% of the total binding of 43.7 nmol/mg protein. Binding of trivalent arsenicals to peptides and proteins can alter their structure and function and contribute to adverse health outcomes such as toxicity and carcinogenicity.