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Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis by Nadine Taudte; Miriam Linnert; Jens-Ulrich Rahfeld; Anke Piechotta; Daniel Ramsbeck; Mirko Buchholz; Petr Kolenko; Christoph Parthier; John A. Houston; Florian Veillard; Sigrun Eick; Jan Potempa; Stephan Schilling; Hans-Ulrich Demuth; Milton T. Stubbs is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer's disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral pathogens Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia represent attractive target enzymes for small-molecule inhibitor development, as their action is likely to stabilize essential periplasmic and outer membrane proteins by N-terminal pyroglutamination. In contrast to other microbial QCs that utilize the so-called type I enzymes, these oral pathogens possess sequences corresponding to type II QCs, observed hitherto only in animals. However, whether differences between these bacteroidal QCs and animal QCs are sufficient to enable development of selective inhibitors is not clear. To learn more, we recombinantly expressed all three QCs. They exhibit comparable catalytic efficiencies and are inhibited by metal chelators. Crystal structures of the enzymes from P. gingivalis (PgQC) and T. forsythia (TfQC) reveal a tertiary structure composed of an eight-stranded β-sheet surrounded by seven α-helices, typical of anim

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Author

Nadine Taudte; Miriam Linnert; Jens-Ulrich Rahfeld; Anke Piechotta; Daniel Ramsbeck; Mirko Buchholz; Petr Kolenko; Christoph Parthier; John A. Houston; Florian Veillard; Sigrun Eick; Jan Potempa; Stephan Schilling; Hans-Ulrich Demuth; Milton T. Stubbs

Publisher

Elsevier BV

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)