NBCZone: Universal Three-dimensional Construction of Eleven Amino Acids near the Catalytic Nucleophile and Base in the Superfamily of (chymo)trypsin-like Serine Fold Proteases
Document Type
Article
Publication Date
2020
Keywords
(Chymo)trypsin-like proteases, Catalytic triad, Structural motif, Structural framework
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.ijbiomac.2020.03.025
Abstract
(Chymo)trypsin-like serine fold proteases belong to the serine/cysteine proteases found in eukaryotes, prokaryotes, and viruses. Their catalytic activity is carried out using a triad of amino acids, a nucleophile, a base, and an acid. For this superfamily of proteases, we propose the existence of a universal 3D structure comprising 11 amino acids near the catalytic nucleophile and base – Nucleophile-Base Catalytic Zone (NBCZone). The comparison of NBCZones among 169 eukaryotic, prokaryotic, and viral (chymo)trypsin-like proteases suggested the existence of 15 distinct groups determined by the combination of amino acids located at two “key” structure-functional positions 54T and 55T near the catalytic base His57T. Most eukaryotic and prokaryotic proteases fell into two major groups, [ST]A and TN. Usually, proteases of [ST]A group contain a disulfide bond between cysteines Cys42T and Cys58T of the NBCZone. In contrast, viral proteases were distributed among seven groups, and lack this disulfide bond. Furthermore, only the [ST]A group of eukaryotic proteases contains glycine at position 43T, which is instrumental for activation of these enzymes. In contrast, due to the side chains of residues at position 43T prokaryotic and viral proteases do not have the ability to carry out the structural transition of the eukaryotic zymogen-zyme type.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
International Journal of Biological Macromolecules, v. 153, p. 399-411
Scholar Commons Citation
Denesyuk, Alexander I.; Johnson, Mark S.; Salo-Ahen, Outi M.H.; Uversky, Vladimir N.; and Denessiouk, Konstantin, "NBCZone: Universal Three-dimensional Construction of Eleven Amino Acids near the Catalytic Nucleophile and Base in the Superfamily of (chymo)trypsin-like Serine Fold Proteases" (2020). Molecular Medicine Faculty Publications. 164.
https://digitalcommons.usf.edu/mme_facpub/164
