4oty

From Proteopedia

(Redirected from 4llz)
Jump to: navigation, search
4oty, resolution 2.35Å ()
Ligands: , ,
Activity: Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of lumiracoxib bound to the apo-mouse-cyclooxygenase-2

Publication Abstract from PubMed

Lumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed a series of lumiracoxib derivatives to identify the structural determinants of substrate-selective inhibition. The hydrogen-bonding potential of the substituents at the ortho positions of the aniline ring dictated the potency and substrate selectivity of the inhibitors. The presence of a 5'-methyl group on the phenylacetic acid ring increased the potency of molecules with a single ortho substituent. Des-fluorolumiracoxib (2) was the most potent and selective inhibitor of endocannabinoid oxygenation. The positioning of critical substituents in the binding site was identified from a 2.35A crystal structure of lumiracoxib bound to COX-2.

Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib., Windsor MA, Valk PL, Xu S, Banerjee S, Marnett LJ, Bioorg Med Chem Lett. 2013 Nov 1;23(21):5860-5864. doi:, 10.1016/j.bmcl.2013.08.097. Epub 2013 Sep 6. PMID:24060487

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

Function

[PGH2_MOUSE] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.[1] [2] [3] [4]

About this Structure

4oty is a 2 chain structure. This structure supersedes the now removed PDB entry 4llz. Full crystallographic information is available from OCA.

Reference

  • Windsor MA, Valk PL, Xu S, Banerjee S, Marnett LJ. Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib. Bioorg Med Chem Lett. 2013 Nov 1;23(21):5860-5864. doi:, 10.1016/j.bmcl.2013.08.097. Epub 2013 Sep 6. PMID:24060487 doi:http://dx.doi.org/10.1016/j.bmcl.2013.08.097
  1. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ. A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. PMID:12925531 doi:http://dx.doi.org/10.1074/jbc.M305481200
  2. Vecchio AJ, Simmons DM, Malkowski MG. Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63. Epub 2010 May 12. PMID:20463020 doi:10.1074/jbc.M110.119867
  3. Duggan KC, Walters MJ, Musee J, Harp JM, Kiefer JR, Oates JA, Marnett LJ. Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen. J Biol Chem. 2010 Nov 5;285(45):34950-9. Epub 2010 Sep 1. PMID:20810665 doi:10.1074/jbc.M110.162982
  4. Vecchio AJ, Malkowski MG. The structural basis of endocannabinoid oxygenation by cyclooxygenase-2. J Biol Chem. 2011 Jun 10;286(23):20736-45. Epub 2011 Apr 13. PMID:21489986 doi:10.1074/jbc.M111.230367

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools