5cox: Difference between revisions

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Revision as of 20:11, 20 March 2008

File:5cox.gif

, resolution 3.0Å

Sites:

, , and

Ligands:

and

Activity:

Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1

Coordinates:

save as pdb, mmCIF, xml

UNINHIBITED MOUSE CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2)

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

5COX is a Single protein structure of sequence from Mus musculus. 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

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OCA

@@ Line 1: / Line 1: @@
-[[Image:5cox.gif|left|200px]]<br /><applet load="5cox" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:5cox.gif|left|200px]]
-caption="5cox, resolution 3.0&Aring;" />
-'''UNINHIBITED MOUSE CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2)'''<br />
+ {{Structure
+|PDB= 5cox |SIZE=350|CAPTION= <scene name='initialview01'>5cox</scene>, resolution 3.0&Aring;
+|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>
+|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> and <scene name='pdbligand=HEM:PROTOPORPHYRIN IX CONTAINING FE'>HEM</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''UNINHIBITED MOUSE CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2)'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-COX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=HEM:'>HEM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5COX OCA].
+COX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5COX OCA].
 ==Reference==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8967954 8967954]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/8967954 8967954]
 [[Category: Mus musculus]]
 [[Category: Prostaglandin-endoperoxide synthase]]
@@ Line 22: / Line 31: @@
 [[Category: dioxygenase]]
 [[Category: inflammation]]
-[[Category: nonsteroidal antiinflammatory drugs]]
+[[Category: nonsteroidal antiinflammatory drug]]
 [[Category: oxidoreductase]]
 [[Category: peroxidase]]
@@ Line 28: / Line 37: @@
 [[Category: prostaglandin synthase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:14:58 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:11:45 2008''