2vya: Difference between revisions
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<StructureSection load='2vya' size='340' side='right'caption='[[2vya]], [[Resolution|resolution]] 2.75Å' scene=''> | <StructureSection load='2vya' size='340' side='right'caption='[[2vya]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vya]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2vya]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VYA FirstGlance]. <br> | ||
</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=PF7:4-(QUINOLIN-3-YLMETHYL)PIPERIDINE-1-CARBOXYLIC+ACID'>PF7</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | </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=PF7:4-(QUINOLIN-3-YLMETHYL)PIPERIDINE-1-CARBOXYLIC+ACID'>PF7</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mt5|1mt5]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1mt5|1mt5]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Amidase Amidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.4 3.5.1.4] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vya OCA], [https://pdbe.org/2vya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vya RCSB], [https://www.ebi.ac.uk/pdbsum/2vya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vya ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
Revision as of 14:49, 30 March 2022
Crystal Structure of fatty acid amide hydrolase conjugated with the drug-like inhibitor PF-750Crystal Structure of fatty acid amide hydrolase conjugated with the drug-like inhibitor PF-750
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe integral membrane enzyme fatty acid amide hydrolase (FAAH) hydrolyzes the endocannabinoid anandamide and related amidated signaling lipids. Genetic or pharmacological inactivation of FAAH produces analgesic, anxiolytic, and antiinflammatory phenotypes but not the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target. Structure-based inhibitor design has, however, been hampered by difficulties in expressing the human FAAH enzyme. Here, we address this problem by interconverting the active sites of rat and human FAAH using site-directed mutagenesis. The resulting humanized rat (h/r) FAAH protein exhibits the inhibitor sensitivity profiles of human FAAH but maintains the high-expression yield of the rat enzyme. We report a 2.75-A crystal structure of h/rFAAH complexed with an inhibitor, N-phenyl-4-(quinolin-3-ylmethyl)piperidine-1-carboxamide (PF-750), that shows strong preference for human FAAH. This structure offers compelling insights to explain the species selectivity of FAAH inhibitors, which should guide future drug design programs. Structure-guided inhibitor design for human FAAH by interspecies active site conversion.,Mileni M, Johnson DS, Wang Z, Everdeen DS, Liimatta M, Pabst B, Bhattacharya K, Nugent RA, Kamtekar S, Cravatt BF, Ahn K, Stevens RC Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12820-4. Epub 2008 Aug 27. PMID:18753625[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Amidase
- Buffalo rat
- Large Structures
- Ahn, K
- Bhattacharya, K
- Cravatt, B F
- Everdeen, D S
- Johnson, D S
- Kamtekar, S
- Liimatta, M
- Mileni, M
- Nugent, R A
- Pabst, B
- Stevens, R C
- Wang, Z
- Chimera
- Covalent
- Drug- like
- Endoplasmic reticulum
- Faah
- Fatty acid amide hydrolyse
- Golgi apparatus
- Humanized
- Hydrolase
- Inhibitor
- Membrane
- Transmembrane