Cyclooxygenase
From Proteopedia
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| + | ==About this structure (1,2)== | ||
| + | PGHSs are bifunctional homodimers. Both COX-1 and COX-2 are membrane-bound enzymes and are present on the lumenal surfaces of the endoplasmic reticulum and of the inner and outer membranes of the nuclear envelope. However, recently, it has been demonstrated in cultured endothelial cells and fibroblasts that a fraction of COX-2 protein is localized to plasma membrane in caveolae-like structures (3). The primary structure of nascent COX-2 is of 604 amino acids and then it is processed into a mature form by removal of signal peptides giving a protein of 587 amino acids. PGHS-2 is variably glycosylated at two to four sites, leading to the formation of doublets or sometimes triplets on SDS-PAGE. Murine PGHS-2 peptide is presumed to be <scene name='SandboxUAM/Mynewscene/1'>N-glycosylated </scene> (N-acetyl-D-glucosamine) three times at Asn56, Asn130, and Asn396. | ||
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<Structure load='5cox' size='500' frame='true' align='right' caption='Unhibited mouse cyclooxygenase' scene='Insert optional scene name here' /> | <Structure load='5cox' size='500' frame='true' align='right' caption='Unhibited mouse cyclooxygenase' scene='Insert optional scene name here' /> | ||
==NSAIDs== | ==NSAIDs== | ||
Revision as of 14:08, 7 December 2010
About this structure (1,2)
PGHSs are bifunctional homodimers. Both COX-1 and COX-2 are membrane-bound enzymes and are present on the lumenal surfaces of the endoplasmic reticulum and of the inner and outer membranes of the nuclear envelope. However, recently, it has been demonstrated in cultured endothelial cells and fibroblasts that a fraction of COX-2 protein is localized to plasma membrane in caveolae-like structures (3). The primary structure of nascent COX-2 is of 604 amino acids and then it is processed into a mature form by removal of signal peptides giving a protein of 587 amino acids. PGHS-2 is variably glycosylated at two to four sites, leading to the formation of doublets or sometimes triplets on SDS-PAGE. Murine PGHS-2 peptide is presumed to be (N-acetyl-D-glucosamine) three times at Asn56, Asn130, and Asn396.
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NSAIDs
| Drug | Coefficient of selectivity (IC50Cox-1/IC50Cox-2) |
|---|---|
| Ketorolac | |
| Naproxen | |
| Ibuprofen | |
| Indometacin | |
| Acetylsalicylic acid | |
| Diclofenac | |
| Valdecoxib | |
| Etoricoxib | |
| Pharmacologic group | Drug |
|---|---|
| Salicylates | Acetylsalicylic acid |
| Propionic | Naproxen |
| Ibuprofen | |
| Para-aminophenols | Paracetamol |
| Indolacetic | Indometacin |
| Pirrolacetic | Ketorolac |
| Phenilacetic | Diclofenac |
| Piranoidacetic | Etodolac |
| Anthranilic | Mefenamic acid |
| Nicotinic | Clonixin |
| Sulfonanilides | Nimesulide |
Reference
- Ghosh N, Chaki R, Mandal V, Mandal SC. COX-2 as a target for cancer chemotherapy. Pharmacol Rep. 2010 Mar-Apr;62(2):233-44. PMID:20508278
- Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145-82. PMID:10966456 doi:10.1146/annurev.biochem.69.1.145
- Rang HP, Dale MM, Ritter JM, Flower RJ. 2008. Pharmacology. Elsevier. 6th edition. 844 p.
- Smith WL, Langenbach R. Why there are two cyclooxygenase isozymes. J Clin Invest. 2001 Jun;107(12):1491-5. PMID:11413152 doi:10.1172/JCI13271
- Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13926-31. Epub 2002 Sep 19. PMID:12242329 doi:10.1073/pnas.162468699
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