PDBsum entry 4z69

Transport protein

PDB id: 4z69

Contents

Protein chains

581 a.a.

Ligands

F15 ×6

PLM ×4

DIF ×4

Waters ×177

PDB id:

4z69

Name:

Transport protein

Title:

Human serum albumin complexed with palmitic acid and diclofenac

Structure:

Serum albumin. Chain: a, i. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: alb, gig20, gig42, pro0903, pro1708, pro2044, pro2619, pro2675, unq696/pro1341. Expressed in: pichia kudriavzevii. Expression_system_taxid: 4909

Resolution:

2.19Å R-factor: 0.229 R-free: 0.293

Authors:

Y.Zhang,F.Yang

Key ref:

Y.Zhang et al. (2015). Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin. Chem Biol Drug Des, 86, 1178-1184. PubMed id: 25958880 DOI: 10.1111/cbdd.12583

Date:

04-Apr-15 Release date: 27-Jan-16

Protein chains

P02768  (ALBU_HUMAN) -  Albumin from Homo sapiens

Seq: 609 a.a.

Struc: 581 a.a.

DOI no: 10.1111/cbdd.12583

Chem Biol Drug Des 86:1178-1184 (2015)

PubMed id: 25958880

Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin.

Y.Zhang, P.Lee, S.Liang, Z.Zhou, X.Wu, F.Yang, H.Liang.

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.