Pollutant-induced modulation in conformation and β-lactamase activity of human serum albumin.
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.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
Ejaz
E
Ahmad
Gulam
G
Rabbani
Nida
N
Zaidi
Basir
B
Ahmad
Rizwan Hasan
RH
Khan
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004785:Environmental Pollutants / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009284:Naphthols / Q000737:chemistry / Q000378:metabolism; D015125:Oxyquinoline / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D058767:Protein Unfolding; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity; D013816:Thermodynamics; D044366:Transition Temperature; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism
D004785:Environmental Pollutants; D009284:Naphthols; D012709:Serum Albumin; C029350:1-naphthol; D015125:Oxyquinoline; D001618:beta-Lactamases; C028405:2-naphthol