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| <StructureSection load='6o5h' size='340' side='right'caption='[[6o5h]], [[Resolution|resolution]] 2.84Å' scene=''> | | <StructureSection load='6o5h' size='340' side='right'caption='[[6o5h]], [[Resolution|resolution]] 2.84Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6o5h]] is a 3 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=6O5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O5H FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6o5h]] is a 3 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=6O5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O5H FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LNJ:4-{4-[(4-methoxyphenyl)methyl]phenyl}-1,3-thiazol-2-amine'>LNJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.84Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LNJ:4-{4-[(4-methoxyphenyl)methyl]phenyl}-1,3-thiazol-2-amine'>LNJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6o5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5h OCA], [https://pdbe.org/6o5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o5h RCSB], [https://www.ebi.ac.uk/pdbsum/6o5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5h ProSAT]</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=6o5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o5h OCA], [http://pdbe.org/6o5h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o5h RCSB], [http://www.ebi.ac.uk/pdbsum/6o5h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o5h ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://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> | | [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> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Activation of the leukotriene A4 hydrolase (LTA4H) aminopeptidase (AP) activity with 4-methoxydiphenylmethane (4MDM) promoted resolution of neutrophil infiltration in a murine cigarette smoke-induced model for emphysematous chronic obstructive pulmonary disease. Recently, 4-(4-benzylphenyl)thiazol-2-amine (ARM1) was published as a ligand for LTA4H with potential anti-inflammatory properties. To investigate the effect of modifier structure on enzyme kinetics of LTA4H, a series of analogues bearing structural features of ARM1 and 4MDM were synthesized using trifluoroborate Suzuki coupling reactions. Following, the 2.8 A X-ray crystal structure of LTA4H complexed with 4-OMe-ARM1, a 4MDM-ARM1 hybrid molecule, was determined. Kinetic analysis showed that ARM1 and related analogues lowered affinity for the enzyme-substrate complex, resulting in a change of mechanism from hyperbolic mixed predominately catalytic activation (HMx(Sp < Ca)A) as observed for 4MDM to a predominately specific activation (HMx(Sp > Ca)A) mechanism. 4-OMe-ARM1 was then shown to dose responsively reduce LTB4 production in human neutrophils.
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| Effect of Modifier Structure on the Activation of Leukotriene A4 Hydrolase Aminopeptidase Activity.,Lee KH, Petruncio G, Shim A, Burdick M, Zhang Z, Shim YM, Noble SM, Paige M J Med Chem. 2019 Nov 21. doi: 10.1021/acs.jmedchem.9b00663. PMID:31751136<ref>PMID:31751136</ref>
| | ==See Also== |
| | | *[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6o5h" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Lee, K H]] | | [[Category: Lee KH]] |
| [[Category: Noble, S M]] | | [[Category: Noble SM]] |
| [[Category: Paige, M]] | | [[Category: Paige M]] |
| [[Category: 4-ome-arm1]]
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| [[Category: Activator]]
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| [[Category: Aminipeptidase]]
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| [[Category: Hydrolase]]
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| [[Category: Leukotriene a4 hydrolase]]
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