4cox: Difference between revisions
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==Overview== | ==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 ... | 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== | ==About this Structure== | ||
4COX is a | 4COX 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 NAG, HEM and IMN as [http://en.wikipedia.org/wiki/ligands ligands]. 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]]. 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] Structure known Active Sites: ACE, CAT, HEM and SUB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=4COX OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: prostaglandin synthase]] | [[Category: prostaglandin synthase]] | ||
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Revision as of 13:39, 5 November 2007
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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 with NAG, HEM and IMN as ligands. The following page contains interesting information on the relation of 4COX with [Cyclooxygenase]. Active as Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1 Structure known Active Sites: ACE, CAT, HEM and SUB. 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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