PuSH - Publikationsserver des Helmholtz Zentrums München: Latency, thermal stability, and identification of an inhibitory compound of mirolysin, a secretory protease of the human periodontopathogen <em>Tannerella forsythia</em>.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Zak, K.M. ; Bostock, M.J. ; Waligorska, I.* ; Thøgersen, I.B.* ; Enghild, J.J.* ; Popowicz, G.M. ; Grudnik, P.* ; Potempa, J.S.* ; Ksiazek, M.*

Latency, thermal stability, and identification of an inhibitory compound of mirolysin, a secretory protease of the human periodontopathogen Tannerella forsythia.

J. Enzyme Inhib. Med. Chem. 36, 1267-1281 (2021)

Verlagsversion

Forschungsdaten

DOI

PMC

	Open Access Gold

Abstract
Metriken
Zusatzinfos

Mirolysin is a secretory protease of Tannerella forsythia, a member of the dysbiotic oral microbiota responsible for periodontitis. In this study, we show that mirolysin latency is achieved by a "cysteine-switch" mechanism exerted by Cys23 in the N-terminal profragment. Mutation of Cys23 shortened the time needed for activation of the zymogen from several days to 5 min. The mutation also decreased the thermal stability and autoproteolysis resistance of promirolysin. Mature mirolysin is a thermophilic enzyme and shows optimal activity at 65 °C. Through NMR-based fragment screening, we identified a small molecule (compound (cpd) 9) that blocks promirolysin maturation and functions as a competitive inhibitor (K_i = 3.2 µM), binding to the S1' subsite of the substrate-binding pocket. Cpd 9 shows superior specificity and does not interact with other T. forsythia proteases or Lys/Arg-specific proteases.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

5.051

1.517