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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 inductio...

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Autores principales: Ahmad, Ejaz, Rabbani, Gulam, Zaidi, Nida, Ahmad, Basir, Khan, Rizwan Hasan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369883/
https://www.ncbi.nlm.nih.gov/pubmed/22685563
http://dx.doi.org/10.1371/journal.pone.0038372
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author Ahmad, Ejaz
Rabbani, Gulam
Zaidi, Nida
Ahmad, Basir
Khan, Rizwan Hasan
author_facet Ahmad, Ejaz
Rabbani, Gulam
Zaidi, Nida
Ahmad, Basir
Khan, Rizwan Hasan
author_sort Ahmad, Ejaz
collection PubMed
description 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.
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spelling pubmed-33698832012-06-08 Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin Ahmad, Ejaz Rabbani, Gulam Zaidi, Nida Ahmad, Basir Khan, Rizwan Hasan PLoS One Research Article 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. Public Library of Science 2012-06-07 /pmc/articles/PMC3369883/ /pubmed/22685563 http://dx.doi.org/10.1371/journal.pone.0038372 Text en Ahmad et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ahmad, Ejaz
Rabbani, Gulam
Zaidi, Nida
Ahmad, Basir
Khan, Rizwan Hasan
Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin
title Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin
title_full Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin
title_fullStr Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin
title_full_unstemmed Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin
title_short Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin
title_sort pollutant-induced modulation in conformation and β-lactamase activity of human serum albumin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369883/
https://www.ncbi.nlm.nih.gov/pubmed/22685563
http://dx.doi.org/10.1371/journal.pone.0038372
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