3rr3

From Proteopedia

Jump to: navigation, search
3rr3, resolution 2.84Å ()
Ligands: , , ,
Gene: Ptgs2, Cox-2, Cox2, Pghs-b, Tis10 (Mus musculus)
Activity: Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Structure of (R)-flurbiprofen bound to mCOX-2

Publication Abstract from PubMed

Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent 'substrate-selective inhibitors' of endocannabinoid oxygenation. Crystal structures of the COX-2-(R)-naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R) enantiomers relative to (S) enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion (DRG) cells. Substrate-selective inhibition provides new tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain.

(R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2., Duggan KC, Hermanson DJ, Musee J, Prusakiewicz JJ, Scheib JL, Carter BD, Banerjee S, Oates JA, Marnett LJ, Nat Chem Biol. 2011 Nov;7(11):803-9. PMID:22053353

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3rr3 is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.

See Also

Reference

  • Duggan KC, Hermanson DJ, Musee J, Prusakiewicz JJ, Scheib JL, Carter BD, Banerjee S, Oates JA, Marnett LJ. (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. Nat Chem Biol. 2011 Nov;7(11):803-9. PMID:22053353

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools