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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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Pollutants interacting to the HSA.(A) The surface view of domain II of HSA (pdb:1AO6). The subdomain IIA (containing Sudlow binding site 1) is green, IIB is blue and IIA-IIB connecting region is red colored. The loop in ribbon view is clearly shown in background; (B) the flexible residues covering 1N (green), 2N (blue) and 8H (red) in site 1 (upper panel) and in site 2 (lower panel) are demonstrating π-π interaction of aromatic residues with these three pollutants; (C) the secondary structures in HSA sequence. The residues involved in HSA-pollutant interaction of Sudlow site 1 and 2 are highlighted in green. These figures are generated from our previous results [9].
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pone-0038372-g002: Pollutants interacting to the HSA.(A) The surface view of domain II of HSA (pdb:1AO6). The subdomain IIA (containing Sudlow binding site 1) is green, IIB is blue and IIA-IIB connecting region is red colored. The loop in ribbon view is clearly shown in background; (B) the flexible residues covering 1N (green), 2N (blue) and 8H (red) in site 1 (upper panel) and in site 2 (lower panel) are demonstrating π-π interaction of aromatic residues with these three pollutants; (C) the secondary structures in HSA sequence. The residues involved in HSA-pollutant interaction of Sudlow site 1 and 2 are highlighted in green. These figures are generated from our previous results [9].

Mentions: We have studied the effect of pollutants on the structure and function of HSA. 1-naphthol (1N), 2-naphthol (2N) and 8-quinolinol (8H) shown in Figure 1 are direct or indirect (metabolite) organic pollutants and their accumulation in body can cause cyanosis, liver damage, nephritis, circulatory collapse and even death. A detailed study on the mode of interaction between HSA and these pollutants has been already performed and reported by our group [9] and the amino acid residues to which the pollutants bind are shown in Figure 2. In the present study, the effects of pollutant binding to HSA have been analyzed by a number of techniques. UV-visible, fluorescence spectroscopy, circular dichroism and dynamic light scattering are used to investigate the structural changes in protein associated with ligand binding. Here, our study offers not only direct proof for ligand-induced conformational alterations in protein, but also a clear understanding of the nature and after effects of these changes.


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)

Pollutants interacting to the HSA.(A) The surface view of domain II of HSA (pdb:1AO6). The subdomain IIA (containing Sudlow binding site 1) is green, IIB is blue and IIA-IIB connecting region is red colored. The loop in ribbon view is clearly shown in background; (B) the flexible residues covering 1N (green), 2N (blue) and 8H (red) in site 1 (upper panel) and in site 2 (lower panel) are demonstrating π-π interaction of aromatic residues with these three pollutants; (C) the secondary structures in HSA sequence. The residues involved in HSA-pollutant interaction of Sudlow site 1 and 2 are highlighted in green. These figures are generated from our previous results [9].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369883&req=5

pone-0038372-g002: Pollutants interacting to the HSA.(A) The surface view of domain II of HSA (pdb:1AO6). The subdomain IIA (containing Sudlow binding site 1) is green, IIB is blue and IIA-IIB connecting region is red colored. The loop in ribbon view is clearly shown in background; (B) the flexible residues covering 1N (green), 2N (blue) and 8H (red) in site 1 (upper panel) and in site 2 (lower panel) are demonstrating π-π interaction of aromatic residues with these three pollutants; (C) the secondary structures in HSA sequence. The residues involved in HSA-pollutant interaction of Sudlow site 1 and 2 are highlighted in green. These figures are generated from our previous results [9].
Mentions: We have studied the effect of pollutants on the structure and function of HSA. 1-naphthol (1N), 2-naphthol (2N) and 8-quinolinol (8H) shown in Figure 1 are direct or indirect (metabolite) organic pollutants and their accumulation in body can cause cyanosis, liver damage, nephritis, circulatory collapse and even death. A detailed study on the mode of interaction between HSA and these pollutants has been already performed and reported by our group [9] and the amino acid residues to which the pollutants bind are shown in Figure 2. In the present study, the effects of pollutant binding to HSA have been analyzed by a number of techniques. UV-visible, fluorescence spectroscopy, circular dichroism and dynamic light scattering are used to investigate the structural changes in protein associated with ligand binding. Here, our study offers not only direct proof for ligand-induced conformational alterations in protein, but also a clear understanding of the nature and after effects of these changes.

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