2xq0: Difference between revisions
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==Structure of yeast LTA4 hydrolase in complex with Bestatin== | ==Structure of yeast LTA4 hydrolase in complex with Bestatin== | ||
<StructureSection load='2xq0' size='340' side='right' caption='[[2xq0]], [[Resolution|resolution]] 1.96Å' scene=''> | <StructureSection load='2xq0' size='340' side='right'caption='[[2xq0]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xq0]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2xq0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XQ0 FirstGlance]. <br> | ||
</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.955Å</td></tr> | ||
<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=CL:CHLORIDE+ION'>CL</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=2xq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xq0 OCA], [https://pdbe.org/2xq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xq0 RCSB], [https://www.ebi.ac.uk/pdbsum/2xq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xq0 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/LKHA4_YEAST LKHA4_YEAST] Aminopeptidase that preferentially cleaves tripeptides. Also has low epoxide hydrolase activity (in vitro). Can hydrolyze an epoxide moiety of LTA(4) to form LTB(4) (in vitro).<ref>PMID:10574934</ref> <ref>PMID:11601994</ref> <ref>PMID:16024909</ref> <ref>PMID:16597475</ref> <ref>PMID:21146536</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 2xq0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2xq0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Haeggstrom | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Hasan | [[Category: Haeggstrom JZ]] | ||
[[Category: Helgstrand | [[Category: Hasan M]] | ||
[[Category: Thunnissen | [[Category: Helgstrand C]] | ||
[[Category: Usyal | [[Category: Thunnissen MMGM]] | ||
[[Category: Usyal H]] | |||
Latest revision as of 11:02, 23 August 2023
Structure of yeast LTA4 hydrolase in complex with BestatinStructure of yeast LTA4 hydrolase in complex with Bestatin
Structural highlights
FunctionLKHA4_YEAST Aminopeptidase that preferentially cleaves tripeptides. Also has low epoxide hydrolase activity (in vitro). Can hydrolyze an epoxide moiety of LTA(4) to form LTB(4) (in vitro).[1] [2] [3] [4] [5] Publication Abstract from PubMedVertebrate leukotriene A(4) hydrolases are bifunctional zinc metalloenzymes with an epoxide hydrolase and an aminopeptidase activity. In contrast, highly homologous enzymes from lower organisms only have the aminopeptidase activity. From sequence comparisons, it is not clear why this difference occurs. In order to obtain more information on the evolutionary relationship between these enzymes and their activities, the structure of a closely related leucine aminopeptidase from Saccharomyces cerevisiae that only shows a very low epoxide hydrolase activity was determined. To investigate the molecular architecture of the active site, the structures of both the native protein and the protein in complex with the aminopeptidase inhibitor bestatin were solved. These structures show a more spacious active site, and the protected cavity in which the labile substrate leukotriene A(4) is bound in the human enzyme is partially obstructed and in other parts is more solvent accessible. Furthermore, the enzyme undergoes induced fit upon binding of the inhibitor bestatin, leading to a movement of the C-terminal domain. The main triggers for the domain movement are a conformational change of Tyr312 and a subtle change in backbone conformation of the PYGAMEN fingerprint region for peptide substrate recognition. This leads to a change in the hydrogen-bonding network pulling the C-terminal domain into a different position. Inasmuch as bestatin is a structural analogue of a leucyl dipeptide and may be regarded as a transition state mimic, our results imply that the enzyme undergoes induced fit during substrate binding and turnover. A Leukotriene A(4) Hydrolase-Related Aminopeptidase from Yeast Undergoes Induced Fit upon Inhibitor Binding.,Helgstrand C, Hasan M, Uysal H, Haeggstrom JZ, Thunnissen MM J Mol Biol. 2010 Dec 10. PMID:21146536[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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