4cox: Difference between revisions

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[[Image:4cox.~~gif~~|left|200px]]

[[Image:4cox.png|left|200px]]

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~~==Overview==~~

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 Structure==

4COX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The following page contains interesting information on the relation of 4COX with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb17_1.html Cyclooxygenase]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COX 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://www.ncbi.nlm.nih.gov/pubmed/8967954 8967954]

[[Category: Cyclooxygenase]]

[[Category: Mus musculus]]

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[[Category: Prostaglandin]]

[[Category: Prostaglandin synthase]]

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-[[Image:4cox.gif|left|200px]]
+[[Image:4cox.png|left|200px]]
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-==Overview==
+{{ABSTRACT_8967954}}
-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 Structure==
 COX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The following page contains interesting information on the relation of 4COX with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb17_1.html Cyclooxygenase]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COX 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://www.ncbi.nlm.nih.gov/pubmed/8967954 8967954]
 [[Category: Cyclooxygenase]]
 [[Category: Mus musculus]]
@@ Line 35: / Line 31: @@
 [[Category: Prostaglandin]]
 [[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 Thu Jun 26 18:29:12 2008''