3ftv: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ftv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FTV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FTV FirstGlance]. <br> | <table><tr><td colspan='2'>[[3ftv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FTV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FTV FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=11X:N-(PYRIDIN-3-YLMETHYL)ANILINE'>11X</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=11X:N-(PYRIDIN-3-YLMETHYL)ANILINE'>11X</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><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fh7|3fh7]], [[3fts|3fts]], [[3ftu|3ftu]], [[3ftw|3ftw]], [[3ftx|3ftx]], [[3fty|3fty]], [[3ftz|3ftz]], [[3fu0|3fu0]], [[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]], [[3ftw|3ftw]], [[3ftx|3ftx]], [[3fty|3fty]], [[3ftz|3ftz]], [[3fu0|3fu0]], [[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><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 Homo sapiens])</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 Homo sapiens])</td></tr> | ||
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ftv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ftv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ftv RCSB], [http://www.ebi.ac.uk/pdbsum/3ftv 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=3ftv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ftv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ftv RCSB], [http://www.ebi.ac.uk/pdbsum/3ftv PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== 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> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 35: | Line 37: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Davies, D R | [[Category: Davies, D R]] | ||
[[Category: Fol]] | [[Category: Fol]] | ||
[[Category: Fragment crystallography]] | [[Category: Fragment crystallography]] | ||
Revision as of 14:33, 25 December 2014
Leukotriene A4 hydrolase in complex with fragment N-(pyridin-3-ylmethyl)anilineLeukotriene A4 hydrolase in complex with fragment N-(pyridin-3-ylmethyl)aniline
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
|
| ||||||||||||||||||||||