5DQF

Horse Serum Albumin (ESA) in complex with Cetirizine

5DQF の概要

• エントリーDOI: 10.2210/pdb5dqf/pdb
• 分子名称: Serum albumin, TETRAETHYLENE GLYCOL, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: albumin, cetirizine, esa, nysgrc, structural genomics, psi-biology, new york structural genomics research consortium, transport protein
• 由来する生物種: Equus caballus (Horse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68077.17

構造登録者

Handing, K.B.,Shabalin, I.G.,Majorek, K.A.,Chruszcz, M.,Almo, S.C.,Minor, W.,New York Structural Genomics Research Consortium (NYSGRC) (登録日: 2015-09-14, 公開日: 2015-12-23, 最終更新日: 2024-11-06)

主引用文献

Handing, K.B.,Shabalin, I.G.,Szlachta, K.,Majorek, K.A.,Minor, W.
Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.
Mol.Immunol., 71:143-151, 2016

PubMed Abstract: Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews.

PubMed: 26896718
DOI: 10.1016/j.molimm.2016.02.003

実験手法

X-RAY DIFFRACTION (2.15 Å)