3fty: Difference between revisions

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-[[Image:3fty.png|left|200px]]
-{{STRUCTURE_3fty|  PDB=3fty  |  SCENE=  }}
+==Leukotriene A4 hydrolase in complex with fragment 3-(benzyloxy)pyridin-2-amine==
+<StructureSection load='3fty' size='340' side='right'caption='[[3fty]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3fty]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FTY 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]] 2.15&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3IP:3-(BENZYLOXY)PYRIDIN-2-AMINE'>3IP</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3fty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fty OCA], [https://pdbe.org/3fty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fty RCSB], [https://www.ebi.ac.uk/pdbsum/3fty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fty ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/LKHA4_HUMAN LKHA4_HUMAN] Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.<ref>PMID:1897988</ref> <ref>PMID:1975494</ref> <ref>PMID:2244921</ref> <ref>PMID:12207002</ref> <ref>PMID:11917124</ref> <ref>PMID:15078870</ref> <ref>PMID:18804029</ref>
+== 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/ft/3fty_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3fty ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+We describe a novel fragment library termed fragments of life (FOL) for structure-based drug discovery. The FOL library includes natural small molecules of life, derivatives thereof, and biaryl protein architecture mimetics. The choice of fragments facilitates the interrogation of protein active sites, allosteric binding sites, and protein-protein interaction surfaces for fragment binding. We screened the FOL library against leukotriene A4 hydrolase (LTA4H) by X-ray crystallography. A diverse set of fragments including derivatives of resveratrol, nicotinamide, and indole were identified as efficient ligands for LTA4H. These fragments were elaborated in a small number of synthetic cycles into potent inhibitors of LTA4H representing multiple novel chemotypes for modulating leukotriene biosynthesis. Analysis of the fragment-bound structures also showed that the fragments comprehensively recapitulated key chemical features and binding modes of several reported LTA4H inhibitors.
-===Leukotriene A4 hydrolase in complex with fragment 3-(benzyloxy)pyridin-2-amine===
+Discovery of Leukotriene A4 Hydrolase Inhibitors Using Metabolomics Biased Fragment Crystallography (dagger).,Davies DR, Mamat B, Magnusson OT, Christensen J, Haraldsson MH, Mishra R, Pease B, Hansen E, Singh J, Zembower D, Kim H, Kiselyov AS, Burgin AB, Gurney ME, Stewart LJ J Med Chem. 2009 Jul 20. PMID:19618939<ref>PMID:19618939</ref>
-{{ABSTRACT_PUBMED_19618939}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3fty" style="background-color:#fffaf0;"></div>
-[[3fty]] is a 1 chain structure of [[Leukotriene A4 Hydrolase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FTY OCA].
 ==See Also==
 *[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019618939</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Davies, D R.]]
+[[Category: Large Structures]]
-[[Category: Fol]]
+[[Category: Davies DR]]
-[[Category: Fragment crystallography]]
-[[Category: Fragments of life]]
-[[Category: Hydrolase]]
-[[Category: Leukotriene a4 hydrolase]]
-[[Category: Leukotriene biosynthesis]]
-[[Category: Lta4h]]
-[[Category: Metal-binding]]
-[[Category: Metalloprotease]]
-[[Category: Multifunctional enzyme]]
-[[Category: Protease]]