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Pollutant-induced modulation in conformation and β-lactamase activity of human serum albumin.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (6), pp. e38372. Date of Electronic Publication: 2012 Jun 07. - Publication Year :
- 2012
-
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.
- Subjects :
- Amino Acid Sequence
Circular Dichroism
Environmental Pollutants metabolism
Humans
Kinetics
Models, Chemical
Models, Molecular
Molecular Sequence Data
Molecular Structure
Naphthols chemistry
Naphthols metabolism
Oxyquinoline chemistry
Oxyquinoline metabolism
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Unfolding
Serum Albumin metabolism
Spectrometry, Fluorescence
Substrate Specificity
Thermodynamics
Transition Temperature
beta-Lactamases metabolism
Environmental Pollutants chemistry
Protein Conformation
Serum Albumin chemistry
beta-Lactamases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22685563
- Full Text :
- https://doi.org/10.1371/journal.pone.0038372