2oyu

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[[Image:2oyu.gif|left|200px]]<br /><applet load="2oyu" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2oyu.gif|left|200px]]
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caption="2oyu, resolution 2.700&Aring;" />
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'''Indomethacin-(S)-alpha-ethyl-ethanolamide bound to Cyclooxygenase-1'''<br />
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{{Structure
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|PDB= 2oyu |SIZE=350|CAPTION= <scene name='initialview01'>2oyu</scene>, resolution 2.700&Aring;
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|SITE=
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|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> and <scene name='pdbligand=HEM:PROTOPORPHYRIN IX CONTAINING FE'>HEM</scene>
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|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]
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|GENE=
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}}
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'''Indomethacin-(S)-alpha-ethyl-ethanolamide bound to Cyclooxygenase-1'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2OYU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with <scene name='pdbligand=BOG:'>BOG</scene>, <scene name='pdbligand=IMS:'>IMS</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OYU OCA].
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2OYU is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OYU OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17656360 17656360]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17656360 17656360]
[[Category: Ovis aries]]
[[Category: Ovis aries]]
[[Category: Prostaglandin-endoperoxide synthase]]
[[Category: Prostaglandin-endoperoxide synthase]]
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[[Category: nsaid]]
[[Category: nsaid]]
[[Category: oxidoreductase]]
[[Category: oxidoreductase]]
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[[Category: pghs]]
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[[Category: pgh]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:06:21 2008''

Revision as of 16:06, 20 March 2008

Image:2oyu.gif


PDB ID 2oyu

Drag the structure with the mouse to rotate
, resolution 2.700Å
Ligands: , and
Activity: Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1
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

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