2ZB3

Crystal structure of mouse 15-ketoprostaglandin delta-13-reductase in complex with NADPH

Summary for 2ZB3

• Entry DOI: 10.2210/pdb2zb3/pdb
• Related: 2ZB4 2ZB7 2ZB8
• Descriptor: Prostaglandin reductase 2, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm (By similarity): Q8VDQ1
• Total number of polymer chains: 1
• Total formula weight: 38943.71

Authors

Wu, Y.H.,Wang, A.H.J.,Ko, T.P.,Guo, R.T.,Hu, S.M.,Chuang, L.M. (deposition date: 2007-10-16, release date: 2008-09-30, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)