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==Leukotriene A4 hydrolase in complex with fragment 4-(4-fluorobenzoyl)pyridine== | ==Leukotriene A4 hydrolase in complex with fragment 4-(4-fluorobenzoyl)pyridine== | ||
<StructureSection load='3fu0' size='340' side='right' caption='[[3fu0]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='3fu0' size='340' side='right' caption='[[3fu0]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3fu0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3fu0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FU0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FU0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=22F:(4-FLUOROPHENYL)(PYRIDIN-4-YL)METHANONE'>22F</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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=22F:(4-FLUOROPHENYL)(PYRIDIN-4-YL)METHANONE'>22F</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fh7|3fh7]], [[3fts|3fts]], [[3ftu|3ftu]], [[3ftv|3ftv]], [[3ftw|3ftw]], [[3ftx|3ftx]], [[3fty|3fty]], [[3ftz|3ftz]], [[3fu3|3fu3]], [[3fu5|3fu5]], [[3fu6|3fu6]], [[3fud|3fud]], [[3fue|3fue]], [[3fuf|3fuf]], [[3fuh|3fuh]], [[3fui|3fui]], [[3fuj|3fuj]], [[3fuk|3fuk]], [[3ful|3ful]], [[3fum|3fum]], [[3fun|3fun]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fh7|3fh7]], [[3fts|3fts]], [[3ftu|3ftu]], [[3ftv|3ftv]], [[3ftw|3ftw]], [[3ftx|3ftx]], [[3fty|3fty]], [[3ftz|3ftz]], [[3fu3|3fu3]], [[3fu5|3fu5]], [[3fu6|3fu6]], [[3fud|3fud]], [[3fue|3fue]], [[3fuf|3fuf]], [[3fuh|3fuh]], [[3fui|3fui]], [[3fuj|3fuj]], [[3fuk|3fuk]], [[3ful|3ful]], [[3fum|3fum]], [[3fun|3fun]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LTA4H, LTA4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LTA4H, LTA4 ([http://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'>[http://en.wikipedia.org/wiki/Leukotriene-A(4)_hydrolase Leukotriene-A(4) hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.6 3.3.2.6] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukotriene-A(4)_hydrolase Leukotriene-A(4) hydrolase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fu0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fu0 RCSB], [http://www.ebi.ac.uk/pdbsum/3fu0 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=3fu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fu0 OCA], [http://pdbe.org/3fu0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fu0 RCSB], [http://www.ebi.ac.uk/pdbsum/3fu0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fu0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 19: | Line 20: | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=3fu0 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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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 3fu0" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Davies, D R]] | [[Category: Davies, D R]] | ||
[[Category: Fol]] | [[Category: Fol]] | ||
Revision as of 14:20, 5 August 2016
Leukotriene A4 hydrolase in complex with fragment 4-(4-fluorobenzoyl)pyridineLeukotriene A4 hydrolase in complex with fragment 4-(4-fluorobenzoyl)pyridine
Structural highlights
Function[LKHA4_HUMAN] Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.[1] [2] [3] [4] [5] [6] [7] 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 PubMedWe 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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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