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

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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 54 T and 55 T near the catalytic base His57 T. 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 Cys42 T and Cys58 T 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 43 T, which is instrumental for activation of these enzymes. In contrast, due to the side chains of residues at position 43 T prokaryotic and viral proteases do not have the ability to carry out the structural transition of the eukaryotic zymogen-zyme type.

Original languageEnglish
Pages (from-to)399–411
JournalInternational Journal of Biological Macromolecules
Volume153
DOIs
Publication statusPublished - 15 Jun 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • Chymo)trypsin-like proteases
  • Catalytic triad
  • Structural framework
  • Structural motif
  • InFlames

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