3lj7
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 3lj7 is ON HOLD Authors: Mileni, M., Stevens, R.C., Kamtekar, S. Description: 3D-CRYSTAL STRUCTURE OF HUMANIZED-RAT FATTY ACID AMIDE HYDROLASE (FAA...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==3D-crystal structure of humanized-rat fatty acid amide hydrolase (FAAH) conjugated with Carbamate inhibitor URB597== | |
| + | <StructureSection load='3lj7' size='340' side='right'caption='[[3lj7]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3lj7]] 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=3LJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LJ7 FirstGlance]. <br> | ||
| + | </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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=OHO:CYCLOHEXANE+AMINOCARBOXYLIC+ACID'>OHO</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=3lj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lj7 OCA], [https://pdbe.org/3lj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lj7 RCSB], [https://www.ebi.ac.uk/pdbsum/3lj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lj7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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). | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lj/3lj7_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lj7 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The endocannabinoid system regulates a wide range of physiological processes including pain, inflammation, and cognitive/emotional states. URB597 is one of the best characterized covalent inhibitors of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH). Here, we report the structure of the FAAH-URB597 complex at 2.3 A resolution. The structure provides insights into mechanistic details of enzyme inactivation and experimental evidence of a previously uncharacterized active site water molecule that likely is involved in substrate deacylation. This water molecule is part of an extensive hydrogen-bonding network and is coordinated indirectly to residues lining the cytosolic port of the enzyme. In order to corroborate our hypothesis concerning the role of this water molecule in FAAH's catalytic mechanism, we determined the structure of FAAH conjugated to a urea-based inhibitor, PF-3845, to a higher resolution (2.4 A) than previously reported. The higher-resolution structure confirms the presence of the water molecule in a virtually identical location in the active site. Examination of the structures of serine hydrolases that are non-homologous to FAAH, such as elastase, trypsin, or chymotrypsin, shows a similarly positioned hydrolytic water molecule and suggests a functional convergence between the amidase signature enzymes and serine proteases. | ||
| - | + | Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation.,Mileni M, Kamtekar S, Wood DC, Benson TE, Cravatt BF, Stevens RC J Mol Biol. 2010 Jul 23;400(4):743-54. Epub 2010 May 21. PMID:20493882<ref>PMID:20493882</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3lj7" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Fatty acid amide hydrolase|Fatty acid amide hydrolase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Kamtekar S]] | ||
| + | [[Category: Mileni M]] | ||
| + | [[Category: Stevens RC]] | ||
Current revision
3D-crystal structure of humanized-rat fatty acid amide hydrolase (FAAH) conjugated with Carbamate inhibitor URB597
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