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[[Image:3chp.png|left|200px]]
==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]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3chp]] 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=3CHP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CHP FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BO:(3S)-3-AMINO-4-OXO-4-[(4-PHENYLMETHOXYPHENYL)AMINO]BUTANOIC+ACID'>4BO</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><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hs6|1hs6]], [[1gw6|1gw6]], [[1h19|1h19]], [[1sqm|1sqm]], [[3cho|3cho]], [[3chq|3chq]], [[3chr|3chr]], [[3chs|3chs]], [[2vj8|2vj8]]</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><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=3chp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3chp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3chp RCSB], [http://www.ebi.ac.uk/pdbsum/3chp PDBsum]</span></td></tr>
<table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <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>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Leukotriene 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.


{{STRUCTURE_3chp|  PDB=3chp  |  SCENE=  }}
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<ref>PMID:18394906</ref>


===Crystal structure of leukotriene a4 hydrolase in complex with (3S)-3-amino-4-oxo-4-[(4-phenylmethoxyphenyl)amino]butanoic acid===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_18394906}}
 
==About this Structure==
[[3chp]] 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=3CHP OCA].


==See Also==
==See Also==
*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]]
*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:018394906</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Adler, M.]]
[[Category: Adler, M.]]

Revision as of 12:03, 29 September 2014

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

3chp is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Related:1hs6, 1gw6, 1h19, 1sqm, 3cho, 3chq, 3chr, 3chs, 2vj8
Gene:LTA4H, LTA4 (Homo sapiens)
Activity:Leukotriene-A(4) hydrolase, with EC number 3.3.2.6
Resources:FirstGlance, OCA, RCSB, PDBsum

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 PubMed

Leukotriene 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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ 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. Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase. Bioorg Med Chem. 2008 May 1;16(9):4963-83. Epub 2008 Mar 20. PMID:18394906 doi:http://dx.doi.org/10.1016/j.bmc.2008.03.042

3chp, resolution 2.10Å

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