Characterization of the housekeeping sortase from the human pathogen Propionibacterium acnes - first investigation of a class F sortase

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Publikationsdatum
2019
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Biochemical Journal
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Verlag / Herausgebende Institution
Portland Press
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Zusammenfassung
Sortase enzymes play an important role in Gram-positive bacteria. They are responsible for the covalent attachment of proteins to the surface of the bacteria and perform this task via a highly sequence-specific transpeptidation reaction. Since these immobilized proteins are often involved in pathogenicity of Gram-positive bacteria, characterization of this type of enzyme is also of medical relevance. Different classes of sortases (A-F) have been found, which recognize characteristic recognition sequences present in substrate proteins. Up to date, sortase A from Staphylococcus aureus, a housekeeping class A sortase, is the most thoroughly studied representative of the sortase family of enzymes. Here we report the in-depth characterization of the class F sortase from Propionibacterium acnes, a class of sortases that has not been investigated before. As Sortase F is the only transpeptidase found in the P. acnes genome, it is the housekeeping sortase of this organism. Sortase F from P. acnes shows a behavior similar to sortases from class A in terms of pH dependence, recognition sequence and catalytic activity; furthermore, its activity is independent of bivalent ions, which contrasts to sortase A from S. aureus We demonstrate that sortase F is useful for protein engineering applications, by producing a site-specifically conjugated homogenous antibody-drug conjugate with a potency similar to that of a conjugate prepared with sortase A. Thus, the detailed characterization presented here will not only enable the development of anti-virulence agents targeting P. acnes but also provides a powerful alternative to sortase A for protein engineering applications. © 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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ISBN
ISSN
0264-6021
1470-8728
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
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Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
DI GIROLAMO, Salvatore und Georg LIPPS, 2019. Characterization of the housekeeping sortase from the human pathogen Propionibacterium acnes - first investigation of a class F sortase. Biochemical Journal. 2019. DOI 10.1042/BCJ20180885. Verfügbar unter: https://irf.fhnw.ch/handle/11654/30352