Papain-like Cysteine Proteinase Zone (PCP-zone) and PCP Structural Catalytic Core (PCP-SCC) of Enzymes with Cysteine Proteinase Fold

Authors

Konstantin Denessiouk, Åbo Akademi University
Vladimir N. Uversky, University of South FloridaFollow
Sergei E. Permyakov, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”
Eugene A. Permyakov, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”
Mark S. Johnson, Åbo Akademi University
Alexander I. Denesyuk, Åbo Akademi University

Document Type

Article

Publication Date

12-2020

Keywords

Papain, Cysteine proteinases, Catalytic triad, Fold, Zone, Structural catalytic core, COVID-19, SARC-CoV-2

DOI

https://doi.org/10.1016/j.ijbiomac.2020.10.022

Abstract

There are several families of cysteine proteinases with different folds – for example the (chymo)trypsin fold family and papain-like fold family – but in both families the hydrolase activity of cysteine proteinases requires a cysteine residue as the catalytic nucleophile. In this work, we have analyzed the topology of the active site regions in 146 three-dimensional structures of proteins belonging to the Papain-like Cysteine Proteinase (PCP) superfamily, which includes papain as a typical representative of this protein superfamily. All analyzed enzymes contain a unique structurally closed conformation – a “PCP-Zone” – which can be divided into two groups, Class A and Class B. Eight structurally conserved amino acids of the PCP-Zone form a common Structural Core. The Structural Core, catalytic nucleophile, catalytic base and residue Xaa – which stabilizes the side-chain conformation of the catalytic base – make up a PCP Structural Catalytic Core (PCP-SCC). The PCP-SCC of Class A and Class B are divided into 5 and 2 types, respectively. Seven variants of the mutual arrangement of the amino-acid side chains of the catalytic triad – nucleophile, base and residue Xaa – within the same fold clearly demonstrate how enzymes with the papain-like fold adapt to the need to perform diverse functions in spite of their limited structural diversity. The roles of both the PCP-Zone of SARS-CoV-2-PLpro described in this study and the NBCZone of SARS-CoV-2-3CLpro presented in our earlier article (Denesyuk AI, Johnson MS, Salo-Ahen OMH, Uversky VN, Denessiouk K. Int J Biol Macromol. 2020;153:399-411) that are in contacts with inhibitors are discussed.

Comments

Article available for free at PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548629/

Citation / Publisher Attribution

International Journal of Biological Macromolecules, v. 165, Part A, p. 1438-1446

Scholar Commons Citation

Denessiouk, Konstantin; Uversky, Vladimir N.; Permyakov, Sergei E.; Permyakov, Eugene A.; Johnson, Mark S.; and Denesyuk, Alexander I., "Papain-like Cysteine Proteinase Zone (PCP-zone) and PCP Structural Catalytic Core (PCP-SCC) of Enzymes with Cysteine Proteinase Fold" (2020). All publications. 74.
https://digitalcommons.usf.edu/usf_fcrc_all/74