The active site of the SGNH hydrolase-like fold proteins: Nucleophile-oxyanion (Nuc-Oxy) and Acid-Base zones

Konstantin Denessiouk; Alexander I Denesyuk; Sergei E Permyakov; Eugene A Permyakov; Mark S Johnson; Vladimir N Uversky

doi:10.1016/j.crstbi.2023.100123

The active site of the SGNH hydrolase-like fold proteins: Nucleophile-oxyanion (Nuc-Oxy) and Acid-Base zones

Curr Res Struct Biol. 2023 Dec 29:7:100123. doi: 10.1016/j.crstbi.2023.100123. eCollection 2024.

Authors

Konstantin Denessiouk^{1

2}, Alexander I Denesyuk^{1

2}, Sergei E Permyakov¹, Eugene A Permyakov¹, Mark S Johnson², Vladimir N Uversky^{1

3}

Affiliations

¹ Institute for Biological Instrumentation of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Pushchino, 142290, Russia.
² Structural Bioinformatics Laboratory, Biochemistry, InFLAMES Research Flagship Center, Faculty of Science and Engineering, Biochemistry, Åbo Akademi University, Turku, 20520, Finland.
³ Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.

Abstract

SGNH hydrolase-like fold proteins are serine proteases with the default Asp-His-Ser catalytic triad. Here, we show that these proteins share two unique conserved structural organizations around the active site: (1) the Nuc-Oxy Zone around the catalytic nucleophile and the oxyanion hole, and (2) the Acid-Base Zone around the catalytic acid and base. The Nuc-Oxy Zone consists of 14 amino acids cross-linked with eight conserved intra- and inter-block hydrogen bonds. The Acid-Base Zone is constructed from a single fragment of the polypeptide chain, which incorporates both the catalytic acid and base, and whose N- and C-terminal residues are linked together by a conserved hydrogen bond. The Nuc-Oxy and Acid-Base Zones are connected by an SHLink, a two-bond conserved interaction from amino acids, adjacent to the catalytic nucleophile and base.

Keywords: Catalytic triad; Nuc–Oxy and Acid–Base zones; Oxyanion hole; SGNH-Hydrolases; SHLink.