View source for 5ni6


==Crystal structure of human LTA4H mutant D375N in complex with LTA4==
<StructureSection load='5ni6' size='340' side='right'caption='[[5ni6]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ni6]] is a 1 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=5NI6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NI6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DJ3:5S-5,6-oxido-7,9-trans-11,14-cis-eicosatetraenoic+acid'>DJ3</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5ni6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ni6 OCA], [https://pdbe.org/5ni6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ni6 RCSB], [https://www.ebi.ac.uk/pdbsum/5ni6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ni6 ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Human leukotriene (LT) A4 hydrolase/aminopeptidase (LTA4H) is a bifunctional enzyme that converts the highly unstable epoxide intermediate LTA4 into LTB4, a potent leukocyte activating agent, while the aminopeptidase activity cleaves and inactivates the chemotactic tripeptide Pro-Gly-Pro. Here, we describe high-resolution crystal structures of LTA4H complexed with LTA4, providing the structural underpinnings of the enzyme's unique epoxide hydrolase (EH) activity, involving Zn2+, Y383, E271, D375, and two catalytic waters. The structures reveal that a single catalytic water is involved in both catalytic activities of LTA4H, alternating between epoxide ring opening and peptide bond hydrolysis, assisted by E271 and E296, respectively. Moreover, we have found two conformations of LTA4H, uncovering significant domain movements. The resulting structural alterations indicate that LTA4 entrance into the active site is a dynamic process that includes rearrangement of three moving domains to provide fast and efficient alignment and processing of the substrate. Thus, the movement of one dynamic domain widens the active site entrance, while another domain acts like a lid, opening and closing access to the hydrophobic tunnel, which accommodates the aliphatic tale of LTA4 during EH reaction. The enzyme-LTA4 complex structures and dynamic domain movements provide critical insights for development of drugs targeting LTA4H.

Capturing LTA4 hydrolase in action: Insights to the chemistry and dynamics of chemotactic LTB4 synthesis.,Stsiapanava A, Samuelsson B, Haeggstrom JZ Proc Natl Acad Sci U S A. 2017 Aug 21. pii: 201710850. doi:, 10.1073/pnas.1710850114. PMID:28827365<ref>PMID:28827365</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ni6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Stsiapanava A]]