4j5p - Revision history

OCA at 15:36, 20 September 2023

2023-09-20T15:36:20Z

←Older revision		Revision as of 15:36, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J5P FirstGlance]. <br>		<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J5P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [https://pdbe.org/4j5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [https://www.ebi.ac.uk/pdbsum/4j5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5p ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [https://pdbe.org/4j5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [https://www.ebi.ac.uk/pdbsum/4j5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5p ProSAT]</span></td></tr>
	</table>		</table>

OCA at 21:33, 16 November 2022

2022-11-16T21:33:52Z

←Older revision		Revision as of 21:33, 16 November 2022
Line 1:		Line 1:

	==Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase==		==Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase==
-	<StructureSection load='4j5p' size='340' side='right' caption='[[4j5p]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4j5p' size='340' side='right'caption='[[4j5p]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4J5P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J5P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wj1\|2wj1]], [[2wj2\|2wj2]], [[3k7f\|3k7f]], [[3k83\|3k83]], [[3k84\|3k84]], [[3pr0\|3pr0]]</td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [https://pdbe.org/4j5p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [https://www.ebi.ac.uk/pdbsum/4j5p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5p ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Faah, Faah1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase Fatty acid amide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.99 3.5.1.99] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [~~http~~://pdbe.org/4j5p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4j5p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5p ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FAAH1_RAT FAAH1_RAT]] Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (By similarity).	+	[https://www.uniprot.org/uniprot/FAAH1_RAT FAAH1_RAT] Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4j5p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4j5p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Fatty acid amide hydrolase\|Fatty acid amide hydrolase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Buffalo rat~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Fatty acid amide hydrolase~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: Boger~~, D L~~]]	+	[[Category: Boger DL]]
-	[[Category: Brown, M]]	+	[[Category: Brown M]]
-	[[Category: Cravatt~~, B F~~]]	+	[[Category: Cravatt BF]]
-	[[Category: Han~~, G W~~]]	+	[[Category: Han GW]]
-	[[Category: Lichtman~~, A H~~]]	+	[[Category: Lichtman AH]]
-	[[Category: McCormick~~, M S~~]]	+	[[Category: McCormick MS]]
-	[[Category: ~~Neal, S T.~~O]]	+	[[Category: O'Neal ST]]
-	[[Category: Otrubova, K]]	+	[[Category: Otrubova K]]
-	[[Category: Stevens~~, R C]]~~	+	[[Category: Stevens RC]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 09:06, 15 November 2017

2017-11-15T09:06:01Z

←Older revision		Revision as of 09:06, 15 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4j5p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4j5p" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Fatty acid amide hydrolase\|Fatty acid amide hydrolase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:11, 5 August 2016

2016-08-05T21:11:17Z

←Older revision		Revision as of 21:11, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase==		==Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase==
	<StructureSection load='4j5p' size='340' side='right' caption='[[4j5p]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4j5p' size='340' side='right' caption='[[4j5p]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J5P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J5P FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wj1\|2wj1]], [[2wj2\|2wj2]], [[3k7f\|3k7f]], [[3k83\|3k83]], [[3k84\|3k84]], [[3pr0\|3pr0]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wj1\|2wj1]], [[2wj2\|2wj2]], [[3k7f\|3k7f]], [[3k83\|3k83]], [[3k84\|3k84]], [[3pr0\|3pr0]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Faah, Faah1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 ~~Rattus norvegicus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Faah, Faah1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase Fatty acid amide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.99 3.5.1.99] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase Fatty acid amide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.99 3.5.1.99] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [http://www.ebi.ac.uk/pdbsum/4j5p PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [http://pdbe.org/4j5p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [http://www.ebi.ac.uk/pdbsum/4j5p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4j5p" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
	[[Category: Fatty acid amide hydrolase]]		[[Category: Fatty acid amide hydrolase]]
-	[[Category: Rattus norvegicus]]
	[[Category: Boger, D L]]		[[Category: Boger, D L]]
	[[Category: Brown, M]]		[[Category: Brown, M]]

OCA at 05:54, 25 December 2014

2014-12-25T05:54:51Z

←Older revision		Revision as of 05:54, 25 December 2014
Line 9:		Line 9:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [http://www.ebi.ac.uk/pdbsum/4j5p PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [http://www.ebi.ac.uk/pdbsum/4j5p PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FAAH1_RAT FAAH1_RAT]] Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 12:15, 21 December 2014

2014-12-21T12:15:29Z

←Older revision		Revision as of 12:15, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4j5p\| PDB=4j5p \| SCENE= }}~~	+	==Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase==
-	===Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase===	+	<StructureSection load='4j5p' size='340' side='right' caption='[[4j5p]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	{~~{ABSTRACT_PUBMED_23581831}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4j5p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J5P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR1:(1S)-1-{5-[5-(BROMOMETHYL)PYRIDIN-2-YL]-1,3-OXAZOL-2-YL}-7-PHENYLHEPTAN-1-OL'>BR1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2wj1\|2wj1]], [[2wj2\|2wj2]], [[3k7f\|3k7f]], [[3k83\|3k83]], [[3k84\|3k84]], [[3pr0\|3pr0]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Faah, Faah1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fatty_acid_amide_hydrolase Fatty acid amide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.99 3.5.1.99] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j5p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j5p RCSB], [http://www.ebi.ac.uk/pdbsum/4j5p PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The design and characterization of alpha-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two alpha-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent noncompetitive inhibition, the cocrystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site. In vivo characterization of the prototypical inhibitors in mice demonstrates that they raise endogenous brain levels of FAAH substrates to a greater extent and for a much longer duration (>6 h) than the reversible inhibitor 2, indicating that the inhibitors accumulate and persist in the brain to completely inhibit FAAH for a prolonged period. Consistent with this behavior and the targeted irreversible enzyme inhibition, 3 reversed cold allodynia in the chronic constriction injury model of neuropathic pain in mice for a sustained period (>6 h) beyond that observed with the reversible inhibitor 2, providing effects that were unchanged over the 1-6 h time course monitored.

-	~~==Function==~~	+	Rational design of Fatty Acid amide hydrolase inhibitors that act by covalently bonding to two active site residues.,Otrubova K, Brown M, McCormick MS, Han GW, O'Neal ST, Cravatt BF, Stevens RC, Lichtman AH, Boger DL J Am Chem Soc. 2013 Apr 24;135(16):6289-99. doi: 10.1021/ja4014997. Epub 2013 Apr, 12. PMID:23581831<ref>PMID:23581831</ref>
-	~~[[http://www.uniprot~~.~~org/uniprot/FAAH1_RAT FAAH1_RAT]] Degrades bioactive fatty acid amides like oleamide~~, ~~the endogenous cannabinoid~~, ~~anandamide and myristic amide to their corresponding acids~~, ~~thereby serving to terminate the signaling functions of these molecules~~. ~~Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates~~ (~~By similarity~~).	+

-	==~~About this Structure~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[~~4j5p~~]] ~~is a 2 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA].~~	+	</div>
		+
		+	==See Also==
		+	*[[Fatty acid amide hydrolase\|Fatty acid amide hydrolase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Fatty acid amide hydrolase]]		[[Category: Fatty acid amide hydrolase]]
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
-	[[Category: Boger, D L.]]	+	[[Category: Boger, D L]]
-	[[Category: Brown, M.]]	+	[[Category: Brown, M]]
-	[[Category: Cravatt, B F.]]	+	[[Category: Cravatt, B F]]
-	[[Category: Han, G W.]]	+	[[Category: Han, G W]]
-	[[Category: Lichtman, A H.]]	+	[[Category: Lichtman, A H]]
-	[[Category: McCormick, M S.]]	+	[[Category: McCormick, M S]]
-	[[Category: Neal, S T.O.]]	+	[[Category: Neal, S T.O]]
-	[[Category: Otrubova, K.]]	+	[[Category: Otrubova, K]]
-	[[Category: Stevens, R C.]]	+	[[Category: Stevens, R C]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 07:40, 2 May 2013

2013-05-02T07:40:05Z

←Older revision		Revision as of 07:40, 2 May 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4j5p\| PDB=4j5p \| SCENE= }}
		+	===Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase===
		+	{{ABSTRACT_PUBMED_23581831}}

-	~~The entry 4j5p is ON HOLD~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/FAAH1_RAT FAAH1_RAT]] Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (By similarity).

-	~~Authors~~: ~~Otrubova, K~~.~~, Brown, M~~.~~, McCormick, M~~.S.~~, Han, G~~.W., ~~O'Neal, S.T~~., Cravatt, B.F., ~~Stevens, R~~.~~C.,~~ Lichtman, A.H., ~~Boger~~, D.L.	+	==About this Structure==
-		+	[[4j5p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5P OCA].
-	~~Description~~: ~~Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide~~ Hydrolase	+	[[Category: Fatty acid amide hydrolase]]
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Boger, D L.]]
		+	[[Category: Brown, M.]]
		+	[[Category: Cravatt, B F.]]
		+	[[Category: Han, G W.]]
		+	[[Category: Lichtman, A H.]]
		+	[[Category: McCormick, M S.]]
		+	[[Category: Neal, S T.O.]]
		+	[[Category: Otrubova, K.]]
		+	[[Category: Stevens, R C.]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA: Protected "4j5p" [edit=sysop:move=sysop]

2013-02-20T13:31:09Z

Protected "4j5p" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:31, 20 February 2013

OCA: New page: '''Unreleased structure''' The entry 4j5p is ON HOLD Authors: Otrubova, K., Brown, M., McCormick, M.S., Han, G.W., O'Neal, S.T., Cravatt, B.F., Stevens, R.C., Lichtman, A.H., Boger, D.L...

2013-02-20T13:31:08Z

New page: '''Unreleased structure''' The entry 4j5p is ON HOLD Authors: Otrubova, K., Brown, M., McCormick, M.S., Han, G.W., O'Neal, S.T., Cravatt, B.F., Stevens, R.C., Lichtman, A.H., Boger, D.L...

New page

'''Unreleased structure'''

The entry 4j5p is ON HOLD

Authors: Otrubova, K., Brown, M., McCormick, M.S., Han, G.W., O'Neal, S.T., Cravatt, B.F., Stevens, R.C., Lichtman, A.H., Boger, D.L.

Description: Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase