Papain-like cysteine proteinase zone (PCP-zone) and PCP structural catalytic core (PCP-SCC) of enzymes with cysteine proteinase fold
| Autor: | Sergei E. Permyakov, Vladimir N. Uversky, Alexander I. Denesyuk, Konstantin Denessiouk, Mark S. Johnson, Eugene A. Permyakov |
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| Rok vydání: | 2020 |
| Předmět: |
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Molecular Stereochemistry 02 engineering and technology Biochemistry Article SARC-CoV-2 03 medical and health sciences chemistry.chemical_compound Structural catalytic core Structural Biology Catalytic Domain Papain Catalytic triad medicine Fold Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology COVID-19 Active site Zone General Medicine Protein superfamily 021001 nanoscience & nanotechnology Trypsin Cysteine proteinases Amino acid Enzyme chemistry Biocatalysis biology.protein 0210 nano-technology medicine.drug Cysteine |
| Zdroj: | International Journal of Biological Macromolecules |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2020.10.022 |
| Popis: | 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. Graphical abstract Unlabelled Image |
| Databáze: | OpenAIRE |
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