title: Paclitaxel-HSA interaction. Binding sites on HSA molecule.
abstract: Paclitaxel (trade name Taxol) is one of the world's most effective anticancer drugs. It is used to treat several cancers including tumours of the breast, ovary and lung. In the present work the interaction of paclitaxel with human serum albumin (HSA) in aqueous solution at physiological pH has been investigated through CD, fluorescence spectroscopy and by the antibody precipitate test. Binding of paclitaxel to albumin impact on protein structure and it influences considerably albumin binding of other molecules like warfarin, heme or bilirubin. The paclitaxel-HSA interaction causes the conformational changes with the loss of helical stability of protein and local perturbation in the domain IIA binding pocket. The relative fluorescence intensity of the paclitaxel-bound HSA decreased, suggesting that perturbation around the Trp 214 residue took place. This was confirmed by the destabilization of the warfarin binding site, which includes Trp 214, and high affinity bilirubin binding site located in subdomain IIA.
authors.affiliation: Faculty of Chemistry, University of Wrocl?aw, F. Joliot-Curie 14, 50-383 Wrocław, Poland. ltl@wchuwr.chem.uni.wroc.pl
authors.forename: Lilianna
authors.initials: L
authors.lastname: Trynda-Lemiesz
mesh_terms: D000941:Antigens / Q000276:immunology; D001663:Bilirubin / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002942:Circular Dichroism; D002945:Cisplatin / Q000494:pharmacology; D006418:Heme / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D017186:Titrimetry; D014859:Warfarin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000941:Antigens; D012709:Serum Albumin; D006418:Heme; D014859:Warfarin; D017239:Paclitaxel; D002945:Cisplatin; D001663:Bilirubin