Journal:Acta Cryst D:S2059798322000948
From Proteopedia
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
| + | The SARS-CoV-2 main protease, Mpro or 3CLpro, is a cysteine peptidase involved in the processing of the two overlapping polyproteins pp1a and pp1ab, with the formation of individual mature non-structural proteins (nsp). Playing a pivotal role in genome replication and transcription, it is a validated antiviral drug target against Covid-19 pandemic. Mpro forms homo-dimers, the only enzymatically active form of the enzyme. Each Mpro protomer is composed of three structural domains; the chymotrypsin- and 3C protease-like domains I and II directly control the catalytic event. The substrate-binding site is between domains I and II, and, at variance with the classical catalytic triad of chymotrypsin-like proteases, SARS-CoV-2 Mpro has a catalytic dyad, consisting of His41 and Cys145. A structural element essential for the catalysis is the so-called “oxyanion loop”, comprising residues 138-145. | ||
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| + | In this paper, we describe a new inactive structure of the main protease of SARS-CoV-2. Movements in the substrate-binding region and near the catalytic site result in a significant reshaping of the reaction center. Consequently, the conformation adopted by residues 139-144 of the oxyanion loop is catalytically-incompetent. Phe140, Leu141 and Asn142 play a major role in the shift between the new inactive and active conformations. The movements of the oxyanion loop and of the N- and C-termini result in the weakening of the dimeric architecture, as evidenced by the decreases in the interaction surface area and in the number of inter-protomer interactions. This novel conformation is relevant both for the comprehension of the mechanism of action of Mpro within the catalytic cycle and for the success of the structure-based drug design of anti-viral drugs. | ||
<b>References</b><br> | <b>References</b><br> | ||
Revision as of 12:08, 1 February 2022
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
