Distribution and diversity of classical deacylases in bacteria.

Autor: Graf LG; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Moreno-Yruela C; Center for Biopharmaceuticals & Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Institute of Chemical Sciences and Engineering (ISIC), School of Basic Sciences (SB), EPFL, Lausanne, Switzerland., Qin C; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Schulze S; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Palm GJ; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Schmöker O; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Wang N; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia., Hocking DM; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia., Jebeli L; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia., Girbardt B; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Berndt L; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Dörre B; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Weis DM; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Janetzky M; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany., Albrecht D; Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany., Zühlke D; Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany., Sievers S; Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany., Strugnell RA; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia., Olsen CA; Center for Biopharmaceuticals & Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hofmann K; Institute for Genetics, University of Cologne, Cologne, Germany., Lammers M; Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany. michael.lammers@uni-greifswald.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 03; Vol. 15 (1), pp. 9496. Date of Electronic Publication: 2024 Nov 03.
DOI: 10.1038/s41467-024-53903-0
Abstrakt: Classical Zn 2+ -dependent deac(et)ylases play fundamental regulatory roles in life and are well characterized in eukaryotes regarding their structures, substrates and physiological roles. In bacteria, however, classical deacylases are less well understood. We construct a Generalized Profile (GP) and identify thousands of uncharacterized classical deacylases in bacteria, which are grouped into five clusters. Systematic structural and functional characterization of representative enzymes from each cluster reveal high functional diversity, including polyamine deacylases and protein deacylases with various acyl-chain type preferences. These data are supported by multiple crystal structures of enzymes from different clusters. Through this extensive analysis, we define the structural requirements of substrate selectivity, and discovered bacterial de-D-/L-lactylases and long-chain deacylases. Importantly, bacterial deacylases are inhibited by archetypal HDAC inhibitors, as supported by co-crystal structures with the inhibitors SAHA and TSA, and setting the ground for drug repurposing strategies to fight bacterial infections. Thus, we provide a systematic structure-function analysis of classical deacylases in bacteria and reveal the basis of substrate specificity, acyl-chain preference and inhibition.
(© 2024. The Author(s).)
Databáze: MEDLINE
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