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

Ahmad E, Rabbani G, Zaidi N, Ahmad B, Khan RH - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

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.

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Secondary structural rearrangements.The far-UV CD spectra of HSA (5 µM) in 1N (A); 2N (B); 8H (C); while in (D) the upper panel corresponds to increase in helical contents whereas lower panel is for increase in 310-helix upon increasing concentration of pollutants.
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pone-0038372-g003: Secondary structural rearrangements.The far-UV CD spectra of HSA (5 µM) in 1N (A); 2N (B); 8H (C); while in (D) the upper panel corresponds to increase in helical contents whereas lower panel is for increase in 310-helix upon increasing concentration of pollutants.

Mentions: It is possible to estimate the secondary structures of a protein using far-UV CD spectra. A positive peak near 190 nm and two negative peaks near 208 and 222 nm are characteristic of a helical protein. From the spectra of Figure 3A to 3C, defined α-helical structures are detected for HSA in absence and presence of pollutants. As the pollutant concentration increased, a notable rearrangement of spectra occurred with increase in major minima due to intramolecular H-bonding rearrangement. These pollutant-induced alterations in secondary structures were quantified by K2D2, an algorithm-based neural network online software [12], [13]. The obtained results are summarized in Table 1. With the increase of pollutant concentrations, a significant increase in the helical structure is observed.


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

Ahmad E, Rabbani G, Zaidi N, Ahmad B, Khan RH - PLoS ONE (2012)

Secondary structural rearrangements.The far-UV CD spectra of HSA (5 µM) in 1N (A); 2N (B); 8H (C); while in (D) the upper panel corresponds to increase in helical contents whereas lower panel is for increase in 310-helix upon increasing concentration of pollutants.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3369883&req=5

pone-0038372-g003: Secondary structural rearrangements.The far-UV CD spectra of HSA (5 µM) in 1N (A); 2N (B); 8H (C); while in (D) the upper panel corresponds to increase in helical contents whereas lower panel is for increase in 310-helix upon increasing concentration of pollutants.
Mentions: It is possible to estimate the secondary structures of a protein using far-UV CD spectra. A positive peak near 190 nm and two negative peaks near 208 and 222 nm are characteristic of a helical protein. From the spectra of Figure 3A to 3C, defined α-helical structures are detected for HSA in absence and presence of pollutants. As the pollutant concentration increased, a notable rearrangement of spectra occurred with increase in major minima due to intramolecular H-bonding rearrangement. These pollutant-induced alterations in secondary structures were quantified by K2D2, an algorithm-based neural network online software [12], [13]. The obtained results are summarized in Table 1. With the increase of pollutant concentrations, a significant increase in the helical structure is observed.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

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.

Show MeSH