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Pollutant-induced modulation in conformation and β-lactamase activity of human serum albumin.

PloS one (2012-06-12)
Ejaz Ahmad, Gulam Rabbani, Nida Zaidi, Basir Ahmad, Rizwan Hasan Khan
ABSTRACT

Structural changes in human serum albumin (HSA) induced by the pollutants 1-naphthol, 2-naphthol and 8-quinolinol were analyzed by circular dichroism, fluorescence spectroscopy and dynamic light scattering. The alteration in protein conformational stability was determined by helical content induction (from 55 to 75%) upon protein-pollutant interactions. Domain plasticity is responsible for the temperature-mediated unfolding of HSA. These findings were compared to HSA-hydrolase activity. We found that though HSA is a monomeric protein, it shows heterotropic allostericity for β-lactamase activity in the presence of pollutants, which act as K- and V-type non-essential activators. Pollutants cause conformational changes and catalytic modifications of the protein (increase in β-lactamase activity from 100 to 200%). HSA-pollutant interactions mediate other protein-ligand interactions, such as HSA-nitrocefin. Therefore, this protein can exist in different conformations with different catalytic properties depending on activator binding. This is the first report to demonstrate the catalytic allostericity of HSA through a mechanistic approach. We also show a correlation with non-microbial drug resistance as HSA is capable of self-hydrolysis of β-lactam drugs, which is further potentiated by pollutants due to conformational changes in HSA.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
1-Naphthol, ReagentPlus®, ≥99%
Sigma-Aldrich
2-Naphthol, 99%
Sigma-Aldrich
2-Naphthol, 98%
Sigma-Aldrich
1-Naphthol, puriss. p.a., reag. Ph. Eur., ≥99% (GC)
Supelco
1-Naphthol, PESTANAL®, analytical standard
Sigma-Aldrich
1-Naphthol, BioXtra, ≥99%
Sigma-Aldrich
2-Naphthol, fluorescence indicator, ≥99.0%
Sigma-Aldrich
2-Naphthol, BioXtra, ≥99.0% (GC)