Crystal structure and catalytic mechanism of the prostaglandin reductase in Mus musculus
Date Issued
2007
Date
2007
Author(s)
Fnag, Chiu-Hao
DOI
en-US
Abstract
The mouse 15-keto-prostaglandin 13-reductase-2, mPGR2, was upregulated during the 3T3-L1 fibroblast differentiation and this enzyme plays a key role in the irreversible degradation of the highly biologically active 15-keto-prostaglandin E2 (15-keto-PGE2).
The mPGR2 consists of 351 amino acids with molecular weight is 38015.3 Da. The mPGR2 cDNA has been cloned and expressed in E. coli system and purified to homogeneity. Enzymatic activity analysis of mPGR2 was completed and the ternary complex structure of mPGR2, NADP+, and 15-keto-PGE2 had also been solved at 2.2 A resolution by X-ray crystallography. The mPGR2 belongs to the medium-chain dehydrogenases/reductases (MDR) superfamily. Catalytic mechanism of mPGR2 was proposed preliminarily based on the structural alignment with human PGR2 (hPGR2) and guinea pig leukotriene B4 12-hydroxydehydrogenase/15-keto-prostaglandin reductase (gpLTB4 12-HD/PGR). Key residues, Y64 and T288 have been identified. Site-directed mutagenesis and activity assays of these mutants revealed that the Y64F and T288L mutants lost 95 % and 40 % catalytic activity, respectively. Together these results reveal structural and functional relationships of mPGR2.
Subjects
前列腺素
還原脢
老鼠
prostaglandin
reductase
mouse
mus musculus
Type
other
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