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Distribution and diversity of classical deacylases in bacteria

Author

Listed:
  • Leonie G. Graf

    (University of Greifswald)

  • Carlos Moreno-Yruela

    (University of Copenhagen
    EPFL)

  • Chuan Qin

    (University of Greifswald)

  • Sabrina Schulze

    (University of Greifswald)

  • Gottfried J. Palm

    (University of Greifswald)

  • Ole Schmöker

    (University of Greifswald)

  • Nancy Wang

    (The University of Melbourne)

  • Dianna M. Hocking

    (The University of Melbourne)

  • Leila Jebeli

    (The University of Melbourne)

  • Britta Girbardt

    (University of Greifswald)

  • Leona Berndt

    (University of Greifswald)

  • Babett Dörre

    (University of Greifswald)

  • Daniel M. Weis

    (University of Greifswald)

  • Markus Janetzky

    (University of Greifswald)

  • Dirk Albrecht

    (University of Greifswald)

  • Daniela Zühlke

    (University of Greifswald)

  • Susanne Sievers

    (University of Greifswald)

  • Richard A. Strugnell

    (The University of Melbourne)

  • Christian A. Olsen

    (University of Copenhagen)

  • Kay Hofmann

    (University of Cologne)

  • Michael Lammers

    (University of Greifswald)

Abstract

Classical Zn2+-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.

Suggested Citation

  • Leonie G. Graf & Carlos Moreno-Yruela & Chuan Qin & Sabrina Schulze & Gottfried J. Palm & Ole Schmöker & Nancy Wang & Dianna M. Hocking & Leila Jebeli & Britta Girbardt & Leona Berndt & Babett Dörre &, 2024. "Distribution and diversity of classical deacylases in bacteria," Nature Communications, Nature, vol. 15(1), pages 1-31, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53903-0
    DOI: 10.1038/s41467-024-53903-0
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    as
    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Fabian Paul & Thomas R Weikl, 2016. "How to Distinguish Conformational Selection and Induced Fit Based on Chemical Relaxation Rates," PLOS Computational Biology, Public Library of Science, vol. 12(9), pages 1-17, September.
    3. Chuan Qin & Leonie G. Graf & Kilian Striska & Markus Janetzky & Norman Geist & Robin Specht & Sabrina Schulze & Gottfried J. Palm & Britta Girbardt & Babett Dörre & Leona Berndt & Stefan Kemnitz & Mar, 2024. "Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    4. Di Zhang & Zhanyun Tang & He Huang & Guolin Zhou & Chang Cui & Yejing Weng & Wenchao Liu & Sunjoo Kim & Sangkyu Lee & Mathew Perez-Neut & Jun Ding & Daniel Czyz & Rong Hu & Zhen Ye & Maomao He & Y. Ge, 2019. "Metabolic regulation of gene expression by histone lactylation," Nature, Nature, vol. 574(7779), pages 575-580, October.
    5. Peter J. Watson & Louise Fairall & Guilherme M. Santos & John W. R. Schwabe, 2012. "Structure of HDAC3 bound to co-repressor and inositol tetraphosphate," Nature, Nature, vol. 481(7381), pages 335-340, January.
    6. Michael S. Finnin & Jill R. Donigian & Alona Cohen & Victoria M. Richon & Richard A. Rifkind & Paul A. Marks & Ronald Breslow & Nikola P. Pavletich, 1999. "Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors," Nature, Nature, vol. 401(6749), pages 188-193, September.
    7. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    8. Peter J. Watson & Christopher J. Millard & Andrew M. Riley & Naomi S. Robertson & Lyndsey C. Wright & Himali Y. Godage & Shaun M. Cowley & Andrew G. Jamieson & Barry V. L. Potter & John W. R. Schwabe, 2016. "Insights into the activation mechanism of class I HDAC complexes by inositol phosphates," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    9. Julija Armalytė & Albinas Čepauskas & Gabija Šakalytė & Julius Martinkus & Jūratė Skerniškytė & Chloé Martens & Edita Sužiedėlienė & Abel Garcia-Pino & Dukas Jurėnas, 2023. "A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Yang Hai & Stephen A. Shinsky & Nicholas J. Porter & David W. Christianson, 2017. "Histone deacetylase 10 structure and molecular function as a polyamine deacetylase," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    11. Daniel Schator & Sonia Mondino & Jérémy Berthelet & Cristina Silvestre & Mathilde Assaya & Christophe Rusniok & Fernando Rodrigues-Lima & Annemarie Wehenkel & Carmen Buchrieser & Monica Rolando, 2023. "Legionella para-effectors target chromatin and promote bacterial replication," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Magdalena Kremer & Sabrina Schulze & Nadja Eisenbruch & Felix Nagel & Robert Vogt & Leona Berndt & Babett Dörre & Gottfried J. Palm & Jens Hoppen & Britta Girbardt & Dirk Albrecht & Susanne Sievers & , 2024. "Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    13. Hanyang Dong & Jianji Zhang & Hui Zhang & Yue Han & Congcong Lu & Chen Chen & Xiaoxia Tan & Siyu Wang & Xue Bai & Guijin Zhai & Shanshan Tian & Tao Zhang & Zhongyi Cheng & Enmin Li & Liyan Xu & Kai Zh, 2022. "YiaC and CobB regulate lysine lactylation in Escherichia coli," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
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