title: Spectroscopic and molecular modeling evidence of clozapine binding to human serum albumin at subdomain IIA.
abstract: Various spectroscopy and molecular docking methods were used to examine the binding of Clozapine (CLZ) to human serum albumin (HSA) in this paper. By monitoring the intrinsic fluorescence of single Trp214 residue and performing Dansylamide (DNSA) displacement measurement, the specific binding of CLZ in the vicinity of Sudlow's Site I of HSA has been clarified. An apparent distance of 27.3 Å between the Trp214 and CLZ was obtained via fluorescence resonance energy transfer (FRET) method. In addition, the changes in the secondary structure of HSA after its complexation with CLZ ligand were studied with CD spectroscopy, which indicate that CLZ does not has remarkable effect on the structure of the protein. Moreover, thermal denaturation experiment shows that the HSA-CLZ complexes are conformationally more stable. Finally, the binding details between CLZ and HSA were further confirmed by molecular docking studies, which revealed that CLZ was bound at subdomain IIA through multiple interactions, such as hydrophobic effect, van der Waals forces and hydrogen bonding.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, People's Republic of China. hz29338@yahoo.com.cn
authors.forename: Xinhu
authors.initials: X
authors.lastname: Wu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xue
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
mesh_terms: D002942:Circular Dichroism; D003024:Clozapine / Q000737:chemistry* / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
chemical_list: D012709:Serum Albumin; D003024:Clozapine