View source for 8j34


==Crystal structure of MERS main protease in complex with PF00835231==
<StructureSection load='8j34' size='340' side='right'caption='[[8j34]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8j34]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8J34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J34 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V2M:~{N}-[(2~{S})-1-[[(2~{S},3~{S})-3,4-bis(oxidanyl)-1-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]butan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]-4-methoxy-1~{H}-indole-2-carboxamide'>V2M</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=8j34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j34 OCA], [https://pdbe.org/8j34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j34 RCSB], [https://www.ebi.ac.uk/pdbsum/8j34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j34 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The main protease (M (pro)) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 M (pro). Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 M (pro) and seven M (pro) mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral M (pro)s. In addition, the crystal structures of SARS-CoV-2 M (pro), SARS-CoV M (pro), MERS-CoV M (pro), and seven SARS-CoV-2 M (pro) mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral M (pro)s. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into M (pro) inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.

Structural basis for the inhibition of coronaviral main proteases by PF-00835231.,Zhou X, Lu X, Lin C, Zou X, Li W, Zeng X, Wang J, Zeng P, Wang W, Zhang J, Jiang H, Li J Acta Biochim Biophys Sin (Shanghai). 2024 Jul 29;56(12):1813-1822. doi: , 10.3724/abbs.2024122. PMID:39076076<ref>PMID:39076076</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8j34" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Middle East respiratory syndrome-related coronavirus]]
[[Category: Li J]]
[[Category: Lin C]]
[[Category: Zhang J]]
[[Category: Zhou XL]]
[[Category: Zou XF]]