3fue: Difference between revisions
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==Leukotriene A4 hydrolase in complex with fragment 5-chloroindole and bestatin== | ==Leukotriene A4 hydrolase in complex with fragment 5-chloroindole and bestatin== | ||
<StructureSection load='3fue' size='340' side='right' caption='[[3fue]], [[Resolution|resolution]] 2.38Å' scene=''> | <StructureSection load='3fue' size='340' side='right' caption='[[3fue]], [[Resolution|resolution]] 2.38Å' scene=''> | ||
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<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='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=3fue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fue OCA], [http://pdbe.org/3fue PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fue RCSB], [http://www.ebi.ac.uk/pdbsum/3fue 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=3fue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fue OCA], [http://pdbe.org/3fue PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fue RCSB], [http://www.ebi.ac.uk/pdbsum/3fue PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fue ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fu/3fue_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fu/3fue_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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[[Category: Human]] | [[Category: Human]] | ||
[[Category: Davies, D R]] | [[Category: Davies, D R]] | ||
[[Category: Alternative splicing]] | |||
[[Category: Cytoplasm]] | |||
[[Category: Fol]] | [[Category: Fol]] | ||
[[Category: Fragment crystallography]] | [[Category: Fragment crystallography]] | ||
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[[Category: Metalloprotease]] | [[Category: Metalloprotease]] | ||
[[Category: Multifunctional enzyme]] | [[Category: Multifunctional enzyme]] | ||
[[Category: Polymorphism]] | |||
[[Category: Protease]] | [[Category: Protease]] | ||
[[Category: Zinc]] | |||
Revision as of 10:28, 5 December 2018
Leukotriene A4 hydrolase in complex with fragment 5-chloroindole and bestatinLeukotriene A4 hydrolase in complex with fragment 5-chloroindole and bestatin
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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