2oyu
From Proteopedia
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|PDB= 2oyu |SIZE=350|CAPTION= <scene name='initialview01'>2oyu</scene>, resolution 2.700Å | |PDB= 2oyu |SIZE=350|CAPTION= <scene name='initialview01'>2oyu</scene>, resolution 2.700Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=IMS:2-[1-(4-CHLOROBENZOYL)-5-METHOXY-2-METHYL-1H-INDOL-3-YL]-N-[(1S)-1-(HYDROXYMETHYL)PROPYL]ACETAMIDE'>IMS</scene> | + | |LIGAND= <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IMS:2-[1-(4-CHLOROBENZOYL)-5-METHOXY-2-METHYL-1H-INDOL-3-YL]-N-[(1S)-1-(HYDROXYMETHYL)PROPYL]ACETAMIDE'>IMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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] | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1pgg|1PGG]], [[1pgf|1PGF]], [[1cqe|1CQE]], [[1eqe|1EQE]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oyu OCA], [http://www.ebi.ac.uk/pdbsum/2oyu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oyu RCSB]</span> | ||
}} | }} | ||
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[[Category: Garavito, R M.]] | [[Category: Garavito, R M.]] | ||
[[Category: Harman, C A.]] | [[Category: Harman, C A.]] | ||
| - | [[Category: BOG]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: IMS]] | ||
[[Category: cox]] | [[Category: cox]] | ||
[[Category: heme]] | [[Category: heme]] | ||
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[[Category: pgh]] | [[Category: pgh]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:25:14 2008'' |
Revision as of 01:25, 31 March 2008
| |||||||
| , resolution 2.700Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Activity: | Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1 | ||||||
| Related: | 1PGG, 1PGF, 1CQE, 1EQE
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Indomethacin-(S)-alpha-ethyl-ethanolamide bound to Cyclooxygenase-1
Overview
The modification of the nonselective nonsteroidal anti-inflammatory drug, indomethacin, by amidation presents a promising strategy for designing novel cyclooxygenase (COX)-2-selective inhibitors. A series of alpha-substituted indomethacin ethanolamides, which exist as R/S-enantiomeric pairs, provides a means to study the impact of stereochemistry on COX inhibition. Comparative studies revealed that the R- and S-enantiomers of the alpha-substituted analogs inhibit COX-2 with almost equal efficacy, whereas COX-1 is selectively inhibited by the S-enantiomers. Mutagenesis studies have not been able to identify residues that manifest the enantioselectivity in COX-1. In an effort to understand the structural impact of chirality on COX-1 selectivity, the crystal structures of ovine COX-1 in complexes with an enantiomeric pair of these indomethacin ethanolamides were determined at resolutions between 2.75 and 2.85 A. These structures reveal unique, enantiomer-selective interactions within the COX-1 side pocket region that stabilize drug binding and account for the chiral selectivity observed with the (S)-alpha-substituted indomethacin ethanolamides. Kinetic analysis of binding demonstrates that both inhibitors bind quickly utilizing a two-step mechanism. However, the second binding step is readily reversible for the R-enantiomer, whereas for the S-enantiomer, it is not. These studies establish for the first time the structural and kinetic basis of high affinity binding of a neutral inhibitor to COX-1 and demonstrate that the side pocket of COX-1, previously thought to be sterically inaccessible, can serve as a binding pocket for inhibitor association.
About this Structure
2OYU is a Single protein structure of sequence from Ovis aries. Full crystallographic information is available from OCA.
Reference
Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-alpha-substituted indomethacin ethanolamides., Harman CA, Turman MV, Kozak KR, Marnett LJ, Smith WL, Garavito RM, J Biol Chem. 2007 Sep 21;282(38):28096-105. Epub 2007 Jul 26. PMID:17656360
Page seeded by OCA on Mon Mar 31 04:25:14 2008
