View source for 8fig


==Room-temperature X-ray structure of SARS-CoV-2 main protease double mutant E290A/R298A in complex with GC373==
<StructureSection load='8fig' size='340' side='right'caption='[[8fig]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fig]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FIG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FIG 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UED:(phenylmethyl)+~{N}-[(2~{S})-4-methyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanyl-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate'>UED</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=8fig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fig OCA], [https://pdbe.org/8fig PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fig RCSB], [https://www.ebi.ac.uk/pdbsum/8fig PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fig ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A critical step for SARS-CoV-2 assembly and maturation involves the autoactivation of the main protease (MPro(WT)) from precursor polyproteins. Upon expression, a model precursor of MPro(WT) mediates its own release at its termini rapidly to yield a mature dimer. A construct with an E290A mutation within MPro exhibits time dependent autoprocessing of the accumulated precursor at the N-terminal nsp4/nsp5 site followed by the C-terminal nsp5/nsp6 cleavage. In contrast, a precursor containing E290A and R298A mutations (MPro(M)) displays cleavage only at the nsp4/nsp5 site to yield an intermediate monomeric product, which is cleaved at the nsp5/nsp6 site only by MPro(WT). MPro(M) and the catalytic domain (MPro(1-199)) fused to the truncated nsp4 region also show time-dependent conversion in vitro to produce MPro(M) and MPro(1-199), respectively. The reactions follow first-order kinetics indicating that the nsp4/nsp5 cleavage occurs via an intramolecular mechanism. These results support a mechanism involving an N-terminal intramolecular cleavage leading to an increase in the dimer population and followed by an intermolecular cleavage at the C-terminus. Thus, targeting the predominantly monomeric MPro precursor for inhibition may lead to the identification of potent drugs for treatment.

Insights into the mechanism of SARS-CoV-2 main protease autocatalytic maturation from model precursors.,Aniana A, Nashed NT, Ghirlando R, Coates L, Kneller DW, Kovalevsky A, Louis JM Commun Biol. 2023 Nov 13;6(1):1159. doi: 10.1038/s42003-023-05469-8. PMID:37957287<ref>PMID:37957287</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8fig" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Coates L]]
[[Category: Kneller DW]]
[[Category: Kovalevsky A]]