title: X-ray crystallographic and fluorometric analysis of the interactions of rhein to human serum albumin.
abstract: To investigate the interactions between natural drugs and human serum albumin (HSA), we performed fluorescence spectroscopy and X-ray crystallography to gain insight into binding mechanism and behaviour of rhein to HSA. Our fluorescence results demonstrated that rhein strongly binds with HSA, and other compounds may affect binding affinity of rhein to different extent. Structural analysis revealed that rhein binds to the IIA subdomain of HSA. The carboxylate group of rhein forms hydrogen bonds with Arg218 and Lys199, as well as a salt bond with Arg222. Hydroxyl group (4) of rhein forms a hydrogen bond with His242, and hydroxyl group (5) of rhein forms a hydrogen bond with Arg257. Oxygen atom (7) of rhein forms a hydrogen bond with Arg222, and oxygen atom (6) of rhein forms a hydrogen bond with H₂O. Furthermore, hydroxyl group (4) of rhein also forms a hydrogen bond with H₂O. Our results reveal the biochemical and structural characteristics of the interaction between rhein and HSA, providing guidance for future development of rhein-based compounds and a drug-HSA delivery system.
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, 541004, Guangxi, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Philbert
authors.initials: P
authors.lastname: Lee
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.forename: ZhiYuan
authors.initials: Z
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005470:Fluorometry; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry
chemical_list: D000880:Anthraquinones; D012709:Serum Albumin; D014867:Water; C020491:rhein
keywords: X-ray crystallography; fluorescence spectroscopy; human serum albumin; protein-drug interaction; rhein