Structural leitmotif and functional variations of the structural catalytic core in (chymo)trypsin-like serine/cysteine fold proteinases
| Autor: | Eugene A. Permyakov, Sergei E. Permyakov, Mark S. Johnson, Konstantin Denessiouk, Vladimir N. Uversky, Alexander I. Denesyuk |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Stereochemistry medicine.medical_treatment 02 engineering and technology Tripeptide Biochemistry Catalysis Serine 03 medical and health sciences Structural Biology Cysteine Proteases Catalytic Domain Catalytic triad medicine Humans Trypsin Amino Acid Sequence Structural motif Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Protease Binding Sites SARS-CoV-2 Serine Endopeptidases COVID-19 General Medicine 021001 nanoscience & nanotechnology Amino acid chemistry Severe acute respiratory syndrome-related coronavirus Serine Proteases 0210 nano-technology medicine.drug Cysteine |
| Zdroj: | International journal of biological macromolecules. 179 |
| ISSN: | 1879-0003 |
| Popis: | Proteinases with the (chymo)trypsin-like serine/cysteine fold comprise a large superfamily performing their function through the Acid – Base – Nucleophile catalytic triad. In our previous work (Denesyuk AI, Johnson MS, Salo-Ahen OMH, Uversky VN, Denessiouk K. Int J Biol Macromol. 2020;153:399–411), we described a universal three-dimensional (3D) structural motif, NBCZone, that contains eleven amino acids: dipeptide 42 T–43 T, pentapeptide 54 T–55 T–56 T–57 T(base)–58 T, tripeptide 195 T(nucleophile)–196 T–197 T and residue 213 T (T – numeration of amino acids in trypsin). The comparison of the NBCZones among the members of the (chymo)trypsin-like protease family suggested the existence of 15 distinct groups. Within each group, the NBCZones incorporate an identical set of conserved interactions and bonds. In the present work, the structural environment of the catalytic acid at the position 102 T and the fourth member of the “catalytic tetrad” at the position 214 T was analyzed in 169 3D structures of proteinases with the (chymo)trypsin-like serine/cysteine fold. We have identified a complete Structural Catalytic Core (SCC) consisting of two classes and four groups. The proteinases belonging to different classes and groups differ from each other by the nature of the interaction between their N- and C-terminal β-barrels. Comparative analysis of the 3CLpro(s) from SARS-CoV-2 and SARS-CoV, used as an example, showed that the amino acids at positions 103 T and 179 T affect the nature of the interaction of the “catalytic acid” core (102 T-Core, N-terminal β-barrel) with the “supplementary” core (S-Core, C-terminal β-barrel), which ultimately results in the modulation of the enzymatic activity. The reported analysis represents an important standalone contribution to the analysis and systematization of the 3D structures of (chymo)trypsin-like serine/cysteine fold proteinases. The use of the developed approach for the comparison of 3D structures will allow, in the event of the appearance of new representatives of a given fold in the PDB, to quickly determine their structural homologues with the identification of possible differences. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect