View source for 7qyh


==Structure of plasmepsin II in complex with 2-aminoquinazolin-4(3H)-one based open-flap inhibitor==
<StructureSection load='7qyh' size='340' side='right'caption='[[7qyh]], [[Resolution|resolution]] 3.33&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qyh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QYH 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]] 3.33&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I0J:2-azanyl-3-[[(2~{R})-oxolan-2-yl]methyl]-7-(5-phenylpentyl)quinazolin-4-one'>I0J</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=7qyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qyh OCA], [https://pdbe.org/7qyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qyh RCSB], [https://www.ebi.ac.uk/pdbsum/7qyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qyh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PLM2_PLAF7 PLM2_PLAF7] During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:29943906). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (By similarity). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).[UniProtKB:P46925]<ref>PMID:29943906</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Selectivity is a major issue in the development of drugs targeting pathogen aspartic proteases. Here, we explore the selectivity-determining factors by studying specifically designed malaria aspartic protease (plasmepsin) open-flap inhibitors. Metadynamics simulations are used to uncover the complex binding/unbinding pathways of these inhibitors and describe the critical transition states in atomistic resolution. The simulation results are compared with experimentally determined enzymatic activities. Our findings demonstrate that plasmepsin inhibitor selectivity can be achieved by targeting the flap loop with hydrophobic substituents that enable ligand binding under the flap loop, as such a behavior is not observed for several other aspartic proteases. The ability to estimate the selectivity of compounds before they are synthesized is of considerable importance in drug design; therefore, we expect that our approach will be useful in selective inhibitor designs against not only aspartic proteases but also other enzyme classes.

Exploring Aspartic Protease Inhibitor Binding to Design Selective Antimalarials.,Bobrovs R, Basens EE, Drunka L, Kanepe I, Matisone S, Velins KK, Andrianov V, Leitis G, Zelencova-Gopejenko D, Rasina D, Jirgensons A, Jaudzems K J Chem Inf Model. 2022 Jul 11;62(13):3263-3273. doi: 10.1021/acs.jcim.2c00422. , Epub 2022 Jun 17. PMID:35712895<ref>PMID:35712895</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qyh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Plasmepsin|Plasmepsin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Bobrovs R]]
[[Category: Jaudzems K]]