7srv

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<StructureSection load='7srv' size='340' side='right'caption='[[7srv]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
<StructureSection load='7srv' size='340' side='right'caption='[[7srv]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7srv]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SRV FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7srv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SRV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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'>[https://en.wikipedia.org/wiki/Leucyl_aminopeptidase Leucyl aminopeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.1 3.4.11.1] </span></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=7srv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7srv OCA], [https://pdbe.org/7srv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7srv RCSB], [https://www.ebi.ac.uk/pdbsum/7srv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7srv ProSAT]</span></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=7srv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7srv OCA], [https://pdbe.org/7srv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7srv RCSB], [https://www.ebi.ac.uk/pdbsum/7srv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7srv ProSAT]</span></td></tr>
</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/Q8IL11_PLAF7 Q8IL11_PLAF7]]
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The metal-dependent M17 aminopeptidases are conserved throughout all kingdoms of life. This large enzyme family is characterized by a conserved binuclear metal center and a distinctive homohexameric arrangement. Recently, we showed that hexamer formation in Plasmodium M17 aminopeptidases was controlled by the metal ion environment, although the functional necessity for hexamer formation is still unclear. To further understand the mechanistic role of the hexameric assembly, here we undertook an investigation of the structure and dynamics of the M17 aminopeptidase from Plasmodium falciparum, PfA-M17. We describe a novel structure of PfA-M17, which shows that the active sites of each trimer are linked by a dynamic loop, and loop movement is coupled with a drastic rearrangement of the binuclear metal center and substrate-binding pocket, rendering the protein inactive. Molecular dynamics simulations and biochemical analyses of PfA-M17 variants demonstrated that this rearrangement is inherent to PfA-M17, and that the transition between the active and inactive states is metal dependent and part of a dynamic regulatory mechanism. Key to the mechanism is a remodeling of the binuclear metal center, which occurs in response to a signal from the neighboring active site and serves to moderate the rate of proteolysis under different environmental conditions. In conclusion, this work identifies a precise mechanism by which oligomerization contributes to PfA-M17 function. Furthermore, it describes a novel role for metal cofactors in the regulation of enzymes, with implications for the wide range of metalloenzymes that operate via a two-metal ion catalytic center, including DNA processing enzymes and metalloproteases.
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A metal ion-dependent conformational switch modulates activity of the Plasmodium M17 aminopeptidase.,Webb CT, Yang W, Riley BT, Hayes BK, Sivaraman KK, Malcolm TR, Harrop S, Atkinson SC, Kass I, Buckle AM, Drinkwater N, McGowan S J Biol Chem. 2022 Jun 9;298(7):102119. doi: 10.1016/j.jbc.2022.102119. PMID:35691342<ref>PMID:35691342</ref>
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==See Also==
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*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
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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 7srv" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Leucyl aminopeptidase]]
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[[Category: Plasmodium falciparum]]
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[[Category: McGowan, S]]
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[[Category: McGowan S]]
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[[Category: Webb, C T]]
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[[Category: Webb CT]]
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[[Category: Enzyme]]
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[[Category: Malaria]]
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[[Category: Metallo aminopeptidase]]
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[[Category: Peptide binding protein]]
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Revision as of 05:27, 8 September 2022

Metal dependent activation of Plasmodium falciparum M17 aminopeptidase (inactive form), spacegroup P22121

PDB ID 7srv

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