2VUE

Human serum albumin complexed with 4Z,15E-bilirubin-IX-alpha

Summary for 2VUE

• Entry DOI: 10.2210/pdb2vue/pdb
• Related: 1AO6 1BJ5 1BKE 1BM0 1E78 1E7A 1E7B 1E7C 1E7E 1E7F 1E7G 1E7H 1E7I 1GNI 1GNJ 1H9Z 1HA2 1HK1 1HK2 1HK3 1HK4 1HK5 1N5U 1O9X 1TF0 1UOR 1YSX 2BX8 2BXA 2BXB 2BXC 2BXD 2BXE 2BXF 2BXG 2BXH 2BXI 2BXK 2BXL 2BXM 2BXN 2BXO 2BXP 2BXQ 2ESG 2VDB 2VUF
• Descriptor: SERUM ALBUMIN, BILIVERDINE IX ALPHA (3 entities in total)
• Functional Keywords: disease mutation, transport protein, alternative splicing, metal-binding, lipid-binding, carrier protein, copper, albumin, secreted, glycation, bilirubin, cleavage on pair of basic residues, polymorphism, drug-binding, glycoprotein
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 134307.73

Authors

Zunszain, P.A.,Ghuman, J.,Curry, S. (deposition date: 2008-05-24, release date: 2008-06-17, Last modification date: 2023-12-13)

Primary citation

Zunszain, P.A.,Ghuman, J.,Mcdonagh, A.F.,Curry, S.
Crystallographic Analysis of Human Serum Albumin Complexed with 4Z,15E-Bilirubin-Ixalpha.
J.Mol.Biol., 381:394-, 2008

PubMed Abstract: Bilirubin, an insoluble yellow-orange pigment derived from heme catabolism, accumulates to toxic levels in individuals with impaired or immature liver function. The resulting jaundice may be managed with phototherapy to isomerize the biosynthetic 4Z,15Z-bilirubin-IXalpha to more soluble and excretable isomers, such as 4Z,15E-bilirubin. Bilirubin and its configurational isomers are transported to the liver by human serum albumin (HSA) but their precise binding location(s) on the protein have yet to be determined. To investigate the molecular details of their interaction, we co-crystallised bilirubin with HSA. Strikingly, the crystal structure--determined to 2.42 A resolution--revealed the 4Z,15E-bilirubin-IXalpha isomer bound to an L-shaped pocket in sub-domain IB. We also determined the co-crystal structure of HSA complexed with fusidic acid, an antibiotic that competitively displaces bilirubin from the protein, and showed that it binds to the same pocket. These results provide the first crystal structure of a natural bilirubin pigment bound to serum albumin, challenge some of the present conceptions about HSA-bilirubin interactions, and provide a sound structural framework for finally resolving the long-standing question of where 4Z,15Z-bilirubin-IXalpha binds to the protein.

PubMed: 18602119
DOI: 10.1016/J.JMB.2008.06.016

Experimental method

X-RAY DIFFRACTION (2.42 Å)