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3qmo, resolution 3.00Å ()
Ligands: , , , , , , ,
Gene: Ptgs2, Cox-2, Cox2, Pghs-b, Tis10 (Mus musculus)
Activity: Prostaglandin-endoperoxide synthase, with EC number
Related: 3hs5, 3hs6, 3hs7, 3ln1, 6cox, 3nt1

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


X-ray crystal structure of NS-398 bound to the cyclooxygenase channel of cyclooxygenase-2

Publication Abstract from PubMed

The cyclooxygenases (COX-1 and COX-2) are membrane-associated, heme-containing homodimers that generate prostaglandin H(2) from arachidonic acid (AA) in the committed step of prostaglandin biogenesis and are the targets for nonsteroidal anti-inflammatory drugs (NSAIDs). N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) was the first in a series of isoform-selective drugs designed to preferentially inhibit COX-2, with the aim of ameliorating many of the toxic gastrointestinal side effects caused by conventional NSAID inhibition. We determined the X-ray crystal structure of murine COX-2 in complex with NS-398 utilizing synchrotron radiation to 3.0A resolution. NS-398 binds in the cyclooxygenase channel in a conformation that is different than that observed for other COX-2-selective inhibitors, such as celecoxib, with no discernible penetration into the side pocket formed in COX-2 by the isoform-specific substitutions of I434V, H513R, and I523V. Instead, the methanesulfonamide moiety of NS-398 interacts with the side chain of Arg-120 at the opening of the cyclooxygenase channel, similar to that observed for acidic, nonselective NSAIDs such as indomethacin and flurbiprofen. Our structure validates inhibitor studies that identified Arg-120 as a molecular determinant for time-dependent inhibition of COX-2 by NS-398.

The structure of NS-398 bound to cyclooxygenase-2., Vecchio AJ, Malkowski MG, J Struct Biol. 2011 Aug 6. PMID:21843643

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

About this Structure

3qmo is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.

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