The unfolding pathway of the defatted human serum albumin (HSA) binding ibuprofen and propofol has been studied by using small-angle X-ray scattering (SAXS) and the support of circular dichroism data. A set of HSA solutions with urea concentrations between 0.00 and 9.00 M was analyzed, and the singular value decomposition method applied to the complete SAXS data set allowed us to distinguish four different states in solution. Besides the native and unfolded forms, two intermediates I1 and I2 have been identified, and the low-resolution structures of these states were obtained by exploiting both ab initio and rigid body fitting methods. The I1 structure was characterized by only one open domain (domain I, which does not host a binding site for either of the ligands), whereas I2 presents only one closed domain (domain III). A direct comparison with the unfolding pathway of the HSA:Ibu complex (Galantini et al. Biophys. Chem. 2010, 147, 111-122) pointed out that the presence of propofol as a second ligand, located in subdomain IIIB, leads to the appearance of an intermediate with two closed domains (domains II and III), which are those that accommodate the ligands. Moreover, the equilibrium between I2 and the unfolded form is slightly shifted toward higher urea concentrations. These results suggest that the cobinding significantly hinders the unfolding process.

Ibuprofen and propofol cobinding effect on human serum albumin unfolding in urea / DEL GIUDICE, Alessandra; Leggio, Claudia; Nicole, Balasco; Galantini, Luciano; Pavel, Nicolae Viorel. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - STAMPA. - 118:34(2014), pp. 10043-10051. [10.1021/jp504280n]

Ibuprofen and propofol cobinding effect on human serum albumin unfolding in urea.

DEL GIUDICE, ALESSANDRA;LEGGIO, Claudia;GALANTINI, Luciano;PAVEL, Nicolae Viorel
2014

Abstract

The unfolding pathway of the defatted human serum albumin (HSA) binding ibuprofen and propofol has been studied by using small-angle X-ray scattering (SAXS) and the support of circular dichroism data. A set of HSA solutions with urea concentrations between 0.00 and 9.00 M was analyzed, and the singular value decomposition method applied to the complete SAXS data set allowed us to distinguish four different states in solution. Besides the native and unfolded forms, two intermediates I1 and I2 have been identified, and the low-resolution structures of these states were obtained by exploiting both ab initio and rigid body fitting methods. The I1 structure was characterized by only one open domain (domain I, which does not host a binding site for either of the ligands), whereas I2 presents only one closed domain (domain III). A direct comparison with the unfolding pathway of the HSA:Ibu complex (Galantini et al. Biophys. Chem. 2010, 147, 111-122) pointed out that the presence of propofol as a second ligand, located in subdomain IIIB, leads to the appearance of an intermediate with two closed domains (domains II and III), which are those that accommodate the ligands. Moreover, the equilibrium between I2 and the unfolded form is slightly shifted toward higher urea concentrations. These results suggest that the cobinding significantly hinders the unfolding process.
ab initio shape reconstruction; small angle x-ray scattering; drug protein binding; protein denaturation; singular value decomposition method; antidenaturant effect
01 Pubblicazione su rivista::01a Articolo in rivista
Ibuprofen and propofol cobinding effect on human serum albumin unfolding in urea / DEL GIUDICE, Alessandra; Leggio, Claudia; Nicole, Balasco; Galantini, Luciano; Pavel, Nicolae Viorel. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - STAMPA. - 118:34(2014), pp. 10043-10051. [10.1021/jp504280n]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/606182
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