2IPW

Crystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acid

2IPW の概要

• エントリーDOI: 10.2210/pdb2ipw/pdb
• 関連するPDBエントリー: 2INE 2INZ 2IQ0 2IQD 2IS7
• 分子名称: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (2,6-DICHLOROPHENYL)ACETIC ACID, ... (4 entities in total)
• 機能のキーワード: tim-barrel, ari, aldo-keto reductase, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P15121
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36660.49

構造登録者

Harrison, D.H.T.,Pape, E.,Brownlee, J.M. (登録日: 2006-10-12, 公開日: 2006-11-28, 最終更新日: 2023-08-30)

主引用文献

Brownlee, J.M.,Carlson, E.,Milne, A.C.,Pape, E.,Harrison, D.H.
Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes.
Bioorg.Chem., 34:424-444, 2006

PubMed Abstract: The competitive inhibition constants of series of inhibitors related to phenylacetic acid against both wild-type and the doubly mutanted C298A/W219Y aldose reductase have been measured. Van't Hoff analysis shows that these acids bind with an enthalpy near -6.8 kcal/mol derived from the electrostatic interactions, while the 100-fold differences in binding affinity appear to be largely due to entropic factors that result from differences in conformational freedom in the unbound state. These temperature studies also point out the difference between substrate and inhibitor binding. X-ray crystallographic analysis of a few of these inhibitor complexes both confirms the importance of a previously described anion binding site and reveals the hydrophobic nature of the primary binding site and its general plasticity. Based on these results, N-glycylthiosuccinimides were synthesized to demonstrate their potential in studies that probe distal binding sites. Reduced alpha-lipoic acid, an anti-oxidant and therapeutic for diabetic complications, was shown to bind aldose reductase with a binding constant of 1 microM.

PubMed: 17083960
DOI: 10.1016/j.bioorg.2006.09.004

実験手法

X-RAY DIFFRACTION (2 Å)