3BHM

Crystal structure of human Carbonyl Reductase 1 in complex with S-hydroxymethylglutathione

3BHM の概要

• エントリーDOI: 10.2210/pdb3bhm/pdb
• 関連するPDBエントリー: 1WMA 2PFG 3BHI 3BHJ
• 分子名称: Carbonyl reductase [NADPH] 1, SULFATE ION, 2-AMINO-4-[1-CARBOXYMETHYL-CARBAMOYL)-2-HYDROXYMETHYLSULFANYL-ETHYLCARBAMOYL]-BUTYRIC ACID, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, acetylation, cytoplasm, nadp, polymorphism
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P16152
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32316.42

構造登録者

Bateman, R.L.,Rauh, D.,Shokat, K.M. (登録日: 2007-11-28, 公開日: 2008-10-21, 最終更新日: 2023-11-01)

主引用文献

Bateman, R.L.,Rauh, D.,Tavshanjian, B.,Shokat, K.M.
Human carbonyl reductase 1 is an s-nitrosoglutathione reductase
J.Biol.Chem., 283:35756-35762, 2008

PubMed Abstract: Human carbonyl reductase 1 (hCBR1) is an NADPH-dependent short chain dehydrogenase/reductase with broad substrate specificity and is thought to be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds including xenobiotics. In addition, hCBR1 possesses a glutathione binding site that allows for increased affinity toward GSH-conjugated molecules. It has been suggested that the GSH-binding site is near the active site; however, no structures with GSH or GSH conjugates have been reported. We have solved the x-ray crystal structures of hCBR1 and a substrate mimic in complex with GSH and the catalytically inert GSH conjugate hydroxymethylglutathione (HMGSH). The structures reveal the GSH-binding site and provide insight into the affinity determinants for GSH-conjugated substrates. We further demonstrate that the structural isostere of HMGSH, S-nitrosoglutathione, is an ideal hCBR1 substrate (Km = 30 microm, kcat = 450 min(-1)) with kinetic constants comparable with the best known hCBR1 substrates. Furthermore, we demonstrate that hCBR1 dependent GSNO reduction occurs in A549 lung adenocarcinoma cell lysates and suggest that hCBR1 may be involved in regulation of tissue levels of GSNO.

PubMed: 18826943
DOI: 10.1074/jbc.M807125200

実験手法

X-RAY DIFFRACTION (1.8 Å)