7k5k: Difference between revisions

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<StructureSection load='7k5k' size='340' side='right'caption='[[7k5k]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
<StructureSection load='7k5k' size='340' side='right'caption='[[7k5k]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7k5k]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemamoeba_vivax Haemamoeba vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K5K FirstGlance]. <br>
<table><tr><td colspan='2'>[[7k5k]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K5K FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.66&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PVC01_120064700, PVP01_1260800 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5855 Haemamoeba vivax])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
<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=7k5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k5k OCA], [https://pdbe.org/7k5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k5k RCSB], [https://www.ebi.ac.uk/pdbsum/7k5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k5k 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=7k5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k5k OCA], [https://pdbe.org/7k5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k5k RCSB], [https://www.ebi.ac.uk/pdbsum/7k5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k5k ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/A5K3U9_PLAVS A5K3U9_PLAVS]
M17 leucyl aminopeptidases are metal-dependent exopeptidases that rely on oligomerization to diversify their functional roles. The M17 aminopeptidases from Plasmodium falciparum (PfA-M17) and Plasmodium vivax (Pv-M17) function as catalytically active hexamers to generate free amino acids from human hemoglobin and are drug targets for the design of novel anti-malarial agents. However, the molecular basis for oligomeric assembly is not fully understood. In this study, we found that the active site metal ions essential for catalytic activity have a secondary structural role mediating the formation of active hexamers. We found that PfA-M17 and Pv-M17 exist in a metal-dependent dynamic equilibrium between active hexameric species and smaller inactive species, that can be controlled by manipulating the identity and concentration of metals available. Mutation of residues involved in metal ion binding impaired catalytic activity and the formation of active hexamers. Structural resolution of Pv-M17 by cryo-electron microscopy and X-ray crystallography together with solution studies revealed that PfA-M17 and Pv-M17 bind metal ions and substrates in a conserved fashion, although Pv-M17 forms the active hexamer more readily and processes substrates faster than PfA-M17. On the basis of these studies, we propose a dynamic equilibrium between monomer dimer tetramer hexamer, which becomes directional towards the large oligomeric states with the addition of metal ions. This sophisticated metal-dependent dynamic equilibrium may apply to other M17 aminopeptidases and underpin the moonlighting capabilities of this enzyme family.


Active site metals mediate an oligomeric equilibrium in Plasmodium M17 aminopeptidases.,Malcolm TR, Belousoff MJ, Venugopal H, Borg NA, Drinkwater N, Atkinson SC, McGowan S J Biol Chem. 2020 Dec 10. pii: RA120.016313. doi: 10.1074/jbc.RA120.016313. PMID:33303633<ref>PMID:33303633</ref>
==See Also==
 
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7k5k" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Haemamoeba vivax]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Leucyl aminopeptidase]]
[[Category: Plasmodium vivax]]
[[Category: Belousoff, M J]]
[[Category: Belousoff MJ]]
[[Category: Malcolm, T R]]
[[Category: Malcolm TR]]
[[Category: McGowan, S]]
[[Category: McGowan S]]
[[Category: Hydrolase]]
[[Category: M17 aminopeptidase]]

Latest revision as of 17:55, 6 March 2024

Plasmodium vivax M17 leucyl aminopeptidase Pv-M17Plasmodium vivax M17 leucyl aminopeptidase Pv-M17

Structural highlights

7k5k is a 6 chain structure with sequence from Plasmodium vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.66Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A5K3U9_PLAVS

See Also

7k5k, resolution 2.66Å

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