title: Unusual binding of a potential biomarker with human serum albumin.
abstract: This study investigates the specific binding of a potential biomarker, [2,2'-bipyridyl]-3,3'-diol (BP(OH)2), with human serum albumin (HSA). The binding of BP(OH)2 at the two primary drug-binding sites on HSA (Sudlow's sites I and II) is explored by a competitive-binding study and monitored by considering the green-light emission from its diketo tautomer. Warfarin is used as a marker for site I and dansyl-L-proline (DP) as a competitor for site II. Steady-state and time-resolved fluorescence measurements affirm that neither of Sudlow's sites is the binding locus of BP(OH)2. To gain an idea regarding the probable binding site of BP(OH)2, we perform molecular-docking studies, which reveal a close proximity of the probe to Trp-214 in subdomain IIA of HSA. Confirmation of this contention is achieved by studying the quenching of the fluorescence of Trp-214 in the presence of BP(OH)2. Moreover, static quenching seems to be responsible for the depletion of the fluorescence of Trp-214, as manifested by the invariance of the intrinsic fluorescence lifetime of Trp-214, as a function of the concentration of BP(OH)2. Based on displacement and quenching studies, supported by molecular docking, we propose that BP(OH)2 binds in a cleft that separates subdomains IIIA and IIB, which is in close proximity to Trp-214.
authors: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India.
authors: Dipanwita
authors: D
authors: De
authors: Harpreet
authors: H
authors: Kaur
authors: Anindya
authors: A
authors: Datta
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D015415:Biomarkers / Q000378:metabolism; D002942:Circular Dichroism; D003619:Dansyl Compounds / Q000737:chemistry; D062105:Molecular Docking Simulation; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014859:Warfarin / Q000737:chemistry / Q000378:metabolism
chemical_list: C499984:(2,2'-bipyridyl)-3,3'-diol; D015415:Biomarkers; D003619:Dansyl Compounds; D012709:Serum Albumin; C086697:dansylproline; D015082:2,2'-Dipyridyl; D014859:Warfarin; D011392:Proline