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4gaa

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==Structure of Leukotriene A4 hydrolase from Xenopus laevis complexed with inhibitor bestatin==
==Structure of Leukotriene A4 hydrolase from Xenopus laevis complexed with inhibitor bestatin==
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<StructureSection load='4gaa' size='340' side='right' caption='[[4gaa]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
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<StructureSection load='4gaa' size='340' side='right'caption='[[4gaa]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4gaa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GAA FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4gaa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAA FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lta4h, MGC78867 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gaa OCA], [https://pdbe.org/4gaa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gaa RCSB], [https://www.ebi.ac.uk/pdbsum/4gaa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gaa ProSAT]</span></td></tr>
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<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=4gaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gaa OCA], [http://pdbe.org/4gaa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gaa RCSB], [http://www.ebi.ac.uk/pdbsum/4gaa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gaa ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q6IP81_XENLA Q6IP81_XENLA]
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Leukotriene A4 hydrolase/aminopeptidase (LTA4H) (EC 3.3.2.6) is a bifunctional zinc metalloenzyme with both an epoxide hydrolase and an aminopeptidase activity. LTA4H from the African claw toad, Xenopus laevis (xlLTA4H) has been shown to, unlike the human enzyme, convert LTA4 to two enzymatic metabolites, LTB4 and another biologically active product Delta(6)-trans-Delta(8)-cis-LTB4 (5(S),12R-dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid). In order to study the molecular aspect of the formation of this product we have characterized the structure and function of xlLTA4H. We solved the structure of xlLTA4H to a resolution of 2.3A. It is a dimeric structure where each monomer has three domains with the active site in between the domains, similar as to the human structure. An important difference between the human and amphibian enzyme is the phenylalanine to tyrosine exchange at position 375. Our studies show that mutating F375 in xlLTA4H to tyrosine abolishes the formation of the LTB4 isomeric product Delta(6)-trans-Delta(8)-cis-LTB4. In an attempt to understand how one amino acid exchange leads to a new product profile as seen in the xlLTA4H, we performed a conformer analysis of the triene part of the substrate LTA4. Our results show that the Boltzmann distribution of substrate conformers correlates with the observed distribution of products. We suggest that the observed difference in product profile between the human and the xlLTA4H arises from different level of discrimination between substrate LTA4 conformers.
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Product formation controlled by substrate dynamics in leukotriene A4 hydrolase.,Stsiapanava A, Tholander F, Kumar RB, Qureshi AA, Niegowski D, Hasan M, Thunnissen M, Haeggstrom JZ, Rinaldo-Matthis A Biochim Biophys Acta. 2014 Feb;1844(2):439-46. doi: 10.1016/j.bbapap.2013.12.003., Epub 2013 Dec 11. PMID:24333438<ref>PMID:24333438</ref>
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==See Also==
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*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4gaa" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: African clawed frog]]
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[[Category: Large Structures]]
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[[Category: Haeggstrom, J Z]]
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[[Category: Xenopus laevis]]
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[[Category: Kumar, R B]]
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[[Category: Haeggstrom JZ]]
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[[Category: Rinaldo-Matthis, A]]
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[[Category: Kumar RB]]
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[[Category: Stsiapanava, A]]
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[[Category: Rinaldo-Matthis A]]
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[[Category: Hydrolase]]
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[[Category: Stsiapanava A]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Leukotriene a4 hydrolase]]
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[[Category: Metalloprotein]]
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[[Category: Protease]]
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[[Category: Zinc binding]]
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Current revision

Structure of Leukotriene A4 hydrolase from Xenopus laevis complexed with inhibitor bestatin

PDB ID 4gaa

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