PDBsum entry 1e7e

Plasma protein

PDB id: 1e7e

Contents

Protein chain

582 a.a. *

Ligands

DKA ×10

Waters ×30

* Residue conservation analysis

PDB id:

1e7e

Name:

Plasma protein

Title:

Human serum albumin complexed with decanoic acid (capric acid)

Structure:

Serum albumin. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: serum. Gene: alb. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932

Resolution:

2.50Å R-factor: 0.220 R-free: 0.271

Authors:

A.A.Bhattacharya,T.Gruene,S.Curry

Key ref:

A.A.Bhattacharya et al. (2000). Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin. J Mol Biol, 303, 721-732. PubMed id: 11061971 DOI: 10.1006/jmbi.2000.4158

Date:

29-Aug-00 Release date: 06-Nov-00

Protein chain

P02768  (ALBU_HUMAN) -  Albumin from Homo sapiens

Seq: 609 a.a.

Struc: 582 a.a.

DOI no: 10.1006/jmbi.2000.4158

J Mol Biol 303:721-732 (2000)

PubMed id: 11061971

Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin.

A.A.Bhattacharya, T.Grüne, S.Curry.

ABSTRACT

Human serum albumin (HSA) is an abundant plasma protein that is responsible for the transport of fatty acids. HSA also binds and perturbs the pharmacokinetics of a wide range of drug compounds. Binding studies have revealed significant interactions between fatty acid and drug-binding sites on albumin but high-resolution structural information on ligand binding to the protein has been lacking. We report here a crystallographic study of five HSA-fatty acid complexes formed using saturated medium-chain and long-chain fatty acids (C10:0, C12:0, C14:0, C16:0 and C18:0). A total of seven binding sites that are occupied by all medium-chain and long-chain fatty acids have been identified, although medium-chain fatty acids are found to bind at additional sites on the protein, yielding a total of 11 distinct binding locations. Comparison of the different complexes reveals key similarities and significant differences in the modes of binding, and serves to rationalise much of the biochemical data on fatty acid interactions with albumin. The two principal drug-binding sites, in sub-domains IIA and IIIA, are observed to be occupied by fatty acids and one of them (in IIIA) appears to coincide with a high-affinity long-chain fatty acid binding site.

Selected figure(s)

Figure 1.
Figure 1. Structures of HSA complexed with five different fatty acids. The protein secondary structure is shown schematically and the domains are colour-coded as follows: I, red; II, green, III, blue. The A and B sub-domains are depicted in dark and light shades, respectively. This colour scheme is maintained throughout. Bound fatty acids are shown in a space-filling representation and coloured by atom type (carbon, grey; oxygen, red). Where two fatty acid molecules bind in close proximity, one of them is shown in a darker shade of grey. All Figures were prepared using Bobscript [Esnouf 1997] and Raster3D [Merrit and Bacon 1997].

Figure 5.
Figure 5. Superposition of fatty acids bound to site 5 in sub-domains IIIB. Amino acid side-chains for Y401 and K525 are shown coloured by atom type.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 303, 721-732) copyright 2000.

Figures were selected by the author.