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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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Related in: MedlinePlus

Thermal scan profiles of HSA in absence and presence of pollutants (1∶5) by CD.The values of (A) θ222 nm for secondary structures and (B) θ263 nm for tertiary structures were plotted against temperature. The insets are plots for the plus derivative of θ (mdeg) with respect to temperature (dθ/dT) versus temperature for the observation of fractional populations of domain specific intermediates.
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pone-0038372-g006: Thermal scan profiles of HSA in absence and presence of pollutants (1∶5) by CD.The values of (A) θ222 nm for secondary structures and (B) θ263 nm for tertiary structures were plotted against temperature. The insets are plots for the plus derivative of θ (mdeg) with respect to temperature (dθ/dT) versus temperature for the observation of fractional populations of domain specific intermediates.

Mentions: HSA is a multidomain protein and its structure is stabilized by different inter-domain interactions. As each of the domains is an autonomous entity for its folding from nascent polypeptide, it is expected that its unfolding will also be independent of other domains. Hence, we have probed unfolding of HSA by means of both secondary and tertiary structures by far-UV CD (at θ222 nm) and near-UV CD (at θ263 nm) respectively. Figure 6A and 6B shows the curves of thermal unfolding transition for HSA in the absence and presence of pollutants. However, it may be possible to populate some intermediates between completely folded helical state and unfolded random state as the thermal unfolding curves are non-overlapping. This prominent non-overlapping of curves are also emphasizing about the fact that the disruption of secondary and tertiary structures in the protein are independent.


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)

Thermal scan profiles of HSA in absence and presence of pollutants (1∶5) by CD.The values of (A) θ222 nm for secondary structures and (B) θ263 nm for tertiary structures were plotted against temperature. The insets are plots for the plus derivative of θ (mdeg) with respect to temperature (dθ/dT) versus temperature for the observation of fractional populations of domain specific intermediates.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038372-g006: Thermal scan profiles of HSA in absence and presence of pollutants (1∶5) by CD.The values of (A) θ222 nm for secondary structures and (B) θ263 nm for tertiary structures were plotted against temperature. The insets are plots for the plus derivative of θ (mdeg) with respect to temperature (dθ/dT) versus temperature for the observation of fractional populations of domain specific intermediates.
Mentions: HSA is a multidomain protein and its structure is stabilized by different inter-domain interactions. As each of the domains is an autonomous entity for its folding from nascent polypeptide, it is expected that its unfolding will also be independent of other domains. Hence, we have probed unfolding of HSA by means of both secondary and tertiary structures by far-UV CD (at θ222 nm) and near-UV CD (at θ263 nm) respectively. Figure 6A and 6B shows the curves of thermal unfolding transition for HSA in the absence and presence of pollutants. However, it may be possible to populate some intermediates between completely folded helical state and unfolded random state as the thermal unfolding curves are non-overlapping. This prominent non-overlapping of curves are also emphasizing about the fact that the disruption of secondary and tertiary structures in the protein are independent.

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
Related in: MedlinePlus