4cku: Difference between revisions
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New page: '''Unreleased structure''' The entry 4cku is ON HOLD Authors: Tars, K., Leitans, J., Jaudzems, K. Description: Three dimensional structure of plasmepsin II in complex with hydroxyethyl... |
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==Three dimensional structure of plasmepsin II in complex with hydroxyethylamine-based inhibitor== | |||
<StructureSection load='4cku' size='340' side='right'caption='[[4cku]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4cku]] 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=4CKU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CKU 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]] 1.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P2F:5-[1,1-BIS(OXIDANYLIDENE)-1,2-THIAZINAN-2-YL]-N3-[(2S,3R)-4-[2-(3-METHOXYPHENYL)PROPAN-2-YLAMINO]-3-OXIDANYL-1-PHENYL-BUTAN-2-YL]-N1,N1-DIPROPYL-BENZENE-1,3-DICARBOXAMIDE'>P2F</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=4cku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cku OCA], [https://pdbe.org/4cku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cku RCSB], [https://www.ebi.ac.uk/pdbsum/4cku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cku ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PLM2_PLAFX PLM2_PLAFX] During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:11782538, PubMed:15574427, PubMed:8844673). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (PubMed:8844673). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).<ref>PMID:11782538</ref> <ref>PMID:15574427</ref> <ref>PMID:8844673</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Antimalarial hit 1 SR (TCMDC-134674) identified in a GlaxoSmithKline cell based screening campaign was evaluated for inhibitory activity against the digestive vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1 SR bound to Plm II was solved, providing structural insight for the design of more potent and selective analogues. Structure-guided optimization led to the identification of structurally simplified analogues 17 and 18 as low nanomolar inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in erythrocytes. | |||
Plasmepsin inhibitory activity and structure-guided optimization of a potent hydroxyethylamine-based antimalarial hit.,Jaudzems K, Tars K, Maurops G, Ivdra N, Otikovs M, Leitans J, Kanepe-Lapsa I, Domraceva I, Mutule I, Trapencieris P, Blackman MJ, Jirgensons A ACS Med Chem Lett. 2014 Jan 13;5(4):373-7. doi: 10.1021/ml4004952. eCollection, 2014 Apr 10. PMID:24900843<ref>PMID:24900843</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cku" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Plasmepsin|Plasmepsin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum]] | |||
[[Category: Jaudzems K]] | |||
[[Category: Leitans J]] | |||
[[Category: Tars K]] | |||
