View source for 7dnc


==Crystal structure of EV71 3C proteinase in complex with a novel inhibitor==
<StructureSection load='7dnc' size='340' side='right'caption='[[7dnc]], [[Resolution|resolution]] 1.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DNC 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]] 1.17&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHR:~{N}-[(2~{S})-3-cyclohexyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]propan-2-yl]-1~{H}-indole-2-carboxamide'>FHR</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=7dnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dnc OCA], [https://pdbe.org/7dnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dnc RCSB], [https://www.ebi.ac.uk/pdbsum/7dnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dnc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel series of peptidomimetic aldehydes was designed and synthesized to target 3C protease (3C(pro)) of enterovirus 71 (EV71). Most of the compounds exhibited high antiviral activity, and among them, compound 18p demonstrated potent enzyme inhibitory activity and broad-spectrum antiviral activity on a panel of enteroviruses and rhinoviruses. The crystal structure of EV71 3C(pro) in complex with 18p determined at a resolution of 1.2 A revealed that 18p covalently linked to the catalytic Cys147 with an aldehyde group. In addition, these compounds also exhibited good inhibitory activity against the 3CL(pro) and the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially compound 18p (IC50 = 0.034 muM, EC50 = 0.29 muM). According to our previous work, these compounds have no reasons for concern regarding acute toxicity. Compared with AG7088, compound 18p also exhibited good pharmacokinetic properties and more potent anticoronavirus activity, making it an excellent lead for further development.

Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2.,Dai W, Jochmans D, Xie H, Yang H, Li J, Su H, Chang D, Wang J, Peng J, Zhu L, Nian Y, Hilgenfeld R, Jiang H, Chen K, Zhang L, Xu Y, Neyts J, Liu H J Med Chem. 2021 Apr 19. doi: 10.1021/acs.jmedchem.0c02258. PMID:33872498<ref>PMID:33872498</ref>

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

==See Also==
*[[Proteinase 3D structures|Proteinase 3D structures]]
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Li MJ]]
[[Category: Su HX]]
[[Category: Xie H]]
[[Category: Xu YC]]