4cox: Difference between revisions

Revision as of 22:22, 4 May 2008

CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, INDOMETHACIN

OverviewOverview

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.

About this StructureAbout this Structure

4COX is a Single protein structure of sequence from Mus musculus. The following page contains interesting information on the relation of 4COX with [Cyclooxygenase]. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents., Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC, Nature. 1996 Dec 19-26;384(6610):644-8. PMID:8967954 Page seeded by OCA on Sun May 4 22:22:19 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:4cox.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 4cox |SIZE=350|CAPTION= <scene name='initialview01'>4cox</scene>, resolution 2.9&Aring;
+The line below this paragraph, containing "STRUCTURE_4cox", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=ACE:SER+530+Is+Acetylated+By+Aspirin+(An+Acetyl+Group+Is+Cov+...'>ACE</scene>, <scene name='pdbsite=CAT:TYR+385+Is+Believed+To+Be+The+Amino+Acid+That+Abstracts+...'>CAT</scene>, <scene name='pdbsite=HEM:HIS+388+Is+The+Axial+Ligand+To+The+Heme'>HEM</scene> and <scene name='pdbsite=SUB:ARG+120+Is+Believed+To+Anchor+The+Carboxylate+Of+Substra+...'>SUB</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_4cox|  PDB=4cox  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cox OCA], [http://www.ebi.ac.uk/pdbsum/4cox PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=4cox RCSB]</span>
-}}
 '''CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, INDOMETHACIN'''
@@ Line 29: / Line 26: @@
 [[Category: Kurumbail, R.]]
 [[Category: Stallings, W.]]
-[[Category: arthritis]]
+[[Category: Arthritis]]
-[[Category: cyclooxygenase]]
+[[Category: Cyclooxygenase]]
-[[Category: dioxygenase]]
+[[Category: Dioxygenase]]
-[[Category: inflammation]]
+[[Category: Inflammation]]
-[[Category: nonsteroidal antiinflammatory drug]]
+[[Category: Nonsteroidal antiinflammatory drug]]
-[[Category: oxidoreductase]]
+[[Category: Oxidoreductase]]
-[[Category: peroxidase]]
+[[Category: Peroxidase]]
-[[Category: prostaglandin]]
+[[Category: Prostaglandin]]
-[[Category: prostaglandin synthase]]
+[[Category: Prostaglandin synthase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 22:22:19 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:38:17 2008''