3PGH: Cyclooxygenase-2 (Prostaglandin Synthase-2) Complexed With A Non- Selective Inhibitor, Flurbiprofen

Citation:
Abstract
Prostaglandins and glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism. Two isoforms of the membrane protein COX are known: COX-1, which is constitutively expressed in most tissues, is responsible for the physiological production of prostaglandins; and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, is responsible for the elevated production of prostaglandins during inflammation. The structure of ovine COX-1 complexed with several NSAIDs has been determined. Here we report the structures of unliganded murine COX-2 and complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, determined at 3.0 to 2.5 A resolution. These structures explain the structural basis for the selective inhibition of COX-2, and demonstrate some of the conformational changes associated with time-dependent inhibition.
PDB ID: 3PGHDownload
MMDB ID: 54594
PDB Deposition Date: 1996/12/18
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 3PGH: dimeric; determined by author and by software (PISA)
Molecular Components in 3PGH
Label Count Molecule
Proteins (2 molecules)
2
Cyclooxygenase-2(Gene symbol: Ptgs2)
Molecule annotation
Chemicals (10 molecules)
1
6
2
2
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.