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2zb4
From Proteopedia
| 2zb4, resolution 1.63Å () | |||||||||
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| Sites: | , , , , and | ||||||||
| Ligands: | , , | ||||||||
| Gene: | PTGR2, ZADH1 (Homo sapiens) | ||||||||
| Activity: | 15-oxoprostaglandin 13-oxidase, with EC number 1.3.1.48 | ||||||||
| Related: | 2zb3, 2zb7, 2zb8 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and 15-keto-PGE2
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.
Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2., Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH, Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2ZB4 is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH. Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2. Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823 doi:10.1016/j.str.2008.09.007
Page seeded by OCA on Tue Feb 17 12:21:57 2009
