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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

Dynamic light scattering of HSA-pollutant complex.Determination of hydrodynamic radii (Rh) of HSA in absence and presence of pollutants.
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pone-0038372-g005: Dynamic light scattering of HSA-pollutant complex.Determination of hydrodynamic radii (Rh) of HSA in absence and presence of pollutants.

Mentions: It was clear from the above findings that upon interaction with pollutants, HSA undergoes conformational changes. The next step is to measure the size of such structural changes. Dynamic light scattering was employed to determine the hydrodynamic radii of native HSA and pollutant-complexed HSA. In Figure 5, the hydrodynamic radii (Rh) of native HSA and HSA in presence of pollutants were calculated as in Table 3. The lower values of polydispersity (5.2–15.1) are indicative of homogenous species in the solution. The Rh value of 4.2 nm for native HSA is in agreement with previous observations [19]. The Rh values of HSA-complexed with pollutants were smaller than the native one. The reduction in hydrodynamic radii upon ligand binding may be due to the “collapsing” of protein around the ligand as it binds. This response may result in a decrease in the molecular volume due to a conformational change such as arabinose binding protein [20], maltose binding protein, calcium binding protein calmodulin and calmodulin-binding domain of calcineurin A [21], [22], D-galactose/D-glucose–binding protein, arginine kinase [23] which “close” on their ligand with a decrease in hydrodynamic volume upon ligand binding. This is also in accordance with another report where the Rh of TehB observed by DLS showed a 20% decrease upon tellurite and S-adenosyl-L-methionine binding [24]. The main reason for reduction in protein size is changes in the local dynamics of the protein, which are perturbed upon ligand interaction.


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)

Dynamic light scattering of HSA-pollutant complex.Determination of hydrodynamic radii (Rh) of HSA in absence and presence of pollutants.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038372-g005: Dynamic light scattering of HSA-pollutant complex.Determination of hydrodynamic radii (Rh) of HSA in absence and presence of pollutants.
Mentions: It was clear from the above findings that upon interaction with pollutants, HSA undergoes conformational changes. The next step is to measure the size of such structural changes. Dynamic light scattering was employed to determine the hydrodynamic radii of native HSA and pollutant-complexed HSA. In Figure 5, the hydrodynamic radii (Rh) of native HSA and HSA in presence of pollutants were calculated as in Table 3. The lower values of polydispersity (5.2–15.1) are indicative of homogenous species in the solution. The Rh value of 4.2 nm for native HSA is in agreement with previous observations [19]. The Rh values of HSA-complexed with pollutants were smaller than the native one. The reduction in hydrodynamic radii upon ligand binding may be due to the “collapsing” of protein around the ligand as it binds. This response may result in a decrease in the molecular volume due to a conformational change such as arabinose binding protein [20], maltose binding protein, calcium binding protein calmodulin and calmodulin-binding domain of calcineurin A [21], [22], D-galactose/D-glucose–binding protein, arginine kinase [23] which “close” on their ligand with a decrease in hydrodynamic volume upon ligand binding. This is also in accordance with another report where the Rh of TehB observed by DLS showed a 20% decrease upon tellurite and S-adenosyl-L-methionine binding [24]. The main reason for reduction in protein size is changes in the local dynamics of the protein, which are perturbed upon ligand interaction.

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