2ZB4

Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and 15-keto-PGE2

2ZB4 の概要

• エントリーDOI: 10.2210/pdb2zb4/pdb
• 関連するPDBエントリー: 2ZB3 2ZB7 2ZB8
• 分子名称: Prostaglandin reductase 2, SULFATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: rossmann fold, alternative splicing, cytoplasm, nadp, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm (By similarity): Q8N8N7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40439.39

構造登録者

Wu, Y.H.,Wang, A.H.J.,Ko, T.P.,Guo, R.T.,Hu, S.M.,Chuang, L.M. (登録日: 2007-10-16, 公開日: 2008-09-30, 最終更新日: 2023-11-01)

主引用文献

Wu, Y.H.,Ko, T.P.,Guo, R.T.,Hu, S.M.,Chuang, L.M.,Wang, A.H.J.
Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.
Structure, 16:1714-1723, 2008

PubMed Abstract: PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha,beta-unsaturated double bond of 15-keto-PGE(2), a key step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. Selective inhibition of PTGR2 may contribute to the improvement of insulin sensitivity with fewer side effects. PTGR2 belongs to the medium-chain dehydrogenase/reductase superfamily. The crystal structures reported here reveal features of the NADPH binding-induced conformational change in a LID motif and a polyproline type II helix which are critical for the reaction. Mutation of Tyr64 and Tyr259 significantly reduces the rate of catalysis but increases the affinity to substrate, confirming the structural observations. Besides targeting cyclooxygenase, indomethacin also inhibits PTGR2 with a binding mode similar to that of 15-keto-PGE(2). The LID motif becomes highly disordered upon the binding of indomethacin, indicating plasticity of the active site. This study has implications for the rational design of inhibitors of PTGR2.

PubMed: 19000823
DOI: 10.1016/j.str.2008.09.007

実験手法

X-RAY DIFFRACTION (1.63 Å)