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==Crystal structure of leukotriene a4 hydrolase in complex with (3S)-3-amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acid== | ==Crystal structure of leukotriene a4 hydrolase in complex with (3S)-3-amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acid== | ||
<StructureSection load='3chp' size='340' side='right' caption='[[3chp]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='3chp' size='340' side='right' caption='[[3chp]], [[Resolution|resolution]] 2.10Å' 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=3chp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3chp OCA], [http://pdbe.org/3chp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3chp RCSB], [http://www.ebi.ac.uk/pdbsum/3chp 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=3chp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3chp OCA], [http://pdbe.org/3chp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3chp RCSB], [http://www.ebi.ac.uk/pdbsum/3chp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3chp 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/ch/3chp_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/3chp_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: Whitlow, M]] | [[Category: Whitlow, M]] | ||
[[Category: Alpha-beta protein]] | [[Category: Alpha-beta protein]] | ||
[[Category: Alternative splicing]] | |||
[[Category: Cytoplasm]] | |||
[[Category: Epoxide hydrolase]] | [[Category: Epoxide hydrolase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
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[[Category: Metalloprotease]] | [[Category: Metalloprotease]] | ||
[[Category: Multifunctional enzyme]] | [[Category: Multifunctional enzyme]] | ||
[[Category: Zinc]] | |||
Revision as of 08:39, 8 March 2018
Crystal structure of leukotriene a4 hydrolase in complex with (3S)-3-amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acidCrystal structure of leukotriene a4 hydrolase in complex with (3S)-3-amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acid
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 PubMedLeukotriene B(4) (LTB(4)) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB(4) and possibly identify novel treatments, inhibitors of the LTB(4) biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria. Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase.,Kirkland TA, Adler M, Bauman JG, Chen M, Haeggstrom JZ, King B, Kochanny MJ, Liang AM, Mendoza L, Phillips GB, Thunnissen M, Trinh L, Whitlow M, Ye B, Ye H, Parkinson J, Guilford WJ Bioorg Med Chem. 2008 May 1;16(9):4963-83. Epub 2008 Mar 20. PMID:18394906[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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