Achieving functionality through modular build-up: Structure and size selection of serine oligopeptidases

Anna J. Kiss-Szemán, Veronika Harmat, Dóra K. Menyhárd

Research output: Review article

1 Citation (Scopus)

Abstract

Enzymes of the prolyl oligopeptidase family (S9 family) recognize their substrates not only by the specificity motif to be cleaved but also by size-they hydrolyze oligopeptides smaller than 30 amino acids. They belong to the serine-protease family, but differ from classical serine-proteases in size (80 kDa), structure (two domains) and regulation system (size selection of substrates). This group of enzymes is an important target for drug design as they are linked to amnesia, schizophrenia, type 2 diabetes, trypanosomiasis, periodontitis and cell growth. By comparing the structure of various members of the family we show that the most important features contributing to selectivity and efficiency are: (i) whether the interactions weaving the two domains together play a role in stabilizing the catalytic triad and thus their absence may provide for its deactivation: these oligopeptidases can screen their substrates by opening up, and (ii) whether the interaction-prone β-edge of the hydrolase domain is accessible and thus can guide a multimerization process that creates shielded entrance or intricate inner channels for the size-based selection of substrates. These cornerstones can be used to estimate the mul-timeric state and selection strategy of yet undetermined structures.

Original languageEnglish
Pages (from-to)1089-1101
Number of pages13
JournalCurrent Protein and Peptide Science
Volume20
Issue number11
DOIs
Publication statusPublished - jan. 1 2019

Fingerprint

Serine
Serine Proteases
prolyl oligopeptidase
Substrates
Oligopeptides
Amnesia
Trypanosomiasis
Periodontitis
Drug Design
Hydrolases
Enzymes
Type 2 Diabetes Mellitus
Schizophrenia
Cell growth
Medical problems
Amino Acids
Growth
oligopeptidase
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Achieving functionality through modular build-up : Structure and size selection of serine oligopeptidases. / Kiss-Szemán, Anna J.; Harmat, Veronika; Menyhárd, Dóra K.

In: Current Protein and Peptide Science, Vol. 20, No. 11, 01.01.2019, p. 1089-1101.

Research output: Review article

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