title: Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin.
abstract: Human serum albumin (HSA) is the most abundant protein in plasma, which plays a central role in drug pharmacokinetics because most compounds bound to HSA in blood circulation. To understand binding characterization of non-steroidal anti-inflammatory drugs to HSA, we resolved the structure of diclofenac and HSA complex by X-ray crystallography. HSA-palmitic acid-diclofenac structure reveals two distinct binding sites for three diclofenac in HSA. One diclofenac is located at the IB subdomain, and its carboxylate group projects toward polar environment, forming hydrogen bond with one water molecule. The other two diclofenac molecules cobind in big hydrophobic cavity of the IIA subdomain without interactive association. Among them, one binds in main chamber of big hydrophobic cavity, and its carboxylate group forms hydrogen bonds with Lys199 and Arg218, as well as one water molecule, whereas another diclofenac binds in side chamber, its carboxylate group projects out cavity, forming hydrogen bond with Ser480.
authors.affiliation: Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
authors.forename: Philbert
authors.initials: P
authors.lastname: Lee
authors.affiliation: Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Shichu
authors.initials: S
authors.lastname: Liang
authors.affiliation: Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory of Ecology of Rare an Endangered Species and Environmental Protection, Ministry of Education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004008:Diclofenac / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012709:Serum Albumin; D004008:Diclofenac
keywords: X-ray crystallography; human serum albumin; non-steroidal anti-inflammatory drug; protein-drug interaction