View source for 3fuf


==Leukotriene A4 hydrolase in complex with fragment 5-fluoroindole and bestatin==
<StructureSection load='3fuf' size='340' side='right'caption='[[3fuf]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3fuf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FUF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=14O:5-FLUORO-1H-INDOLE'>14O</scene>, <scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3fh7|3fh7]], [[3fts|3fts]], [[3ftu|3ftu]], [[3ftv|3ftv]], [[3ftw|3ftw]], [[3ftx|3ftx]], [[3fty|3fty]], [[3ftz|3ftz]], [[3fu0|3fu0]], [[3fu3|3fu3]], [[3fu5|3fu5]], [[3fu6|3fu6]], [[3fud|3fud]], [[3fuh|3fuh]], [[3fui|3fui]], [[3fuj|3fuj]], [[3fuk|3fuk]], [[3ful|3ful]], [[3fum|3fum]], [[3fun|3fun]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LTA4H, LTA4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Leukotriene-A(4)_hydrolase Leukotriene-A(4) hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.6 3.3.2.6] </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=3fuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fuf OCA], [https://pdbe.org/3fuf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fuf RCSB], [https://www.ebi.ac.uk/pdbsum/3fuf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fuf 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/fu/3fuf_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=3fuf 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3fuf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Davies, D R]]
[[Category: Alternative splicing]]
[[Category: Cytoplasm]]
[[Category: Fol]]
[[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: Polymorphism]]
[[Category: Protease]]
[[Category: Zinc]]