6zeq
From Proteopedia
(Difference between revisions)
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==Aspergillus oryzae Leucine Aminopeptidase A mature enzyme== | ==Aspergillus oryzae Leucine Aminopeptidase A mature enzyme== | ||
| - | <StructureSection load='6zeq' size='340' side='right'caption='[[6zeq]]' scene=''> | + | <StructureSection load='6zeq' size='340' side='right'caption='[[6zeq]], [[Resolution|resolution]] 1.97Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZEQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zeq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_oryzae_RIB40 Aspergillus oryzae RIB40]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZEQ FirstGlance]. <br> |
| - | </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=6zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zeq OCA], [https://pdbe.org/6zeq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zeq RCSB], [https://www.ebi.ac.uk/pdbsum/6zeq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zeq ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.97Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zeq OCA], [https://pdbe.org/6zeq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zeq RCSB], [https://www.ebi.ac.uk/pdbsum/6zeq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zeq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LAPA_ASPOR LAPA_ASPOR] Extracellular aminopeptidase that allows assimilation of proteinaceous substrates.<ref>PMID:20803144</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Leucyl aminopeptidase A from Aspergillus oryzae RIB40 (AO-LapA) is an exo-acting peptidase, widely utilised in food debittering applications. AO-LapA is secreted as a zymogen by the host and requires enzymatic cleavage of the autoinhibitory propeptide to reveal its full activity. Scarcity of structural data of zymogen aminopeptidases hampers a better understanding of the details of their molecular action of autoinhibition and how this might be utilised to improve the properties of such enzymes by recombinant methods for more effective bioprocessing. To address this gap in the literature, herein we report high-resolution crystal structures of recombinantly expressed AO-LapA precursor (AO-proLapA), mature LapA (AO-mLapA) and AO-mLapA complexed with reaction product l-leucine (AO-mLapA-Leu), all purified from Pichia pastoris culture supernatant. Our structures reveal a plausible molecular mechanism of LapA catalytic domain autoinhibition by propeptide and highlights the role of intramolecular chaperone (IMC). Our data suggest an absolute requirement for IMC in the maturation of cognate catalytic domain of AO-LapA. This observation is reinforced by our expression and refolding data of catalytic domain only (AO-refLapA) from Escherichia coli inclusion bodies, revealing a limited active conformation. Our work supports the notion that known synthetic aminopeptidase inhibitors and substrates mimic key polar contacts between propeptide and corresponding catalytic domain, demonstrated in our AO-proLapA zymogen crystal structure. Furthermore, understanding the atomic details of the autoinhibitory mechanism of cognate catalytic domains by native propeptides has wider reaching implications toward synthetic production of more effective inhibitors of bimetallic aminopeptidases and other dizinc enzymes that share an analogous reaction mechanism. | ||
| + | |||
| + | The role of propeptide-mediated autoinhibition and intermolecular chaperone in the maturation of cognate catalytic domain in leucine aminopeptidase.,Baltulionis G, Blight M, Robin A, Charalampopoulos D, Watson KA J Struct Biol. 2021 May 12;213(3):107741. doi: 10.1016/j.jsb.2021.107741. PMID:33989771<ref>PMID:33989771</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zeq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Aspergillus oryzae RIB40]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Baltulionis G]] | [[Category: Baltulionis G]] | ||
[[Category: Watson KA]] | [[Category: Watson KA]] | ||
Revision as of 13:48, 24 January 2024
Aspergillus oryzae Leucine Aminopeptidase A mature enzyme
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