Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases

Research output: Contribution to journalArticle


Enzymes with a protein kinase fold transfer phosphate from adenosine 5'-triphosphate (ATP) to substrates in a process known as phosphorylation. Here, we show that the Legionella meta-effector SidJ adopts a protein kinase fold, yet unexpectedly catalyzes protein polyglutamylation. SidJ is activated by host-cell calmodulin to polyglutamylate the SidE family of ubiquitin (Ub) ligases. Crystal structures of the SidJ-calmodulin complex reveal a protein kinase fold that catalyzes ATP-dependent isopeptide bond formation between the amino group of free glutamate and the γ-carboxyl group of an active-site glutamate in SidE. We show that SidJ polyglutamylation of SidE, and the consequent inactivation of Ub ligase activity, is required for successful Legionella replication in a viable eukaryotic host cell.


  • Miles H. Black
  • Adam Osinski
  • Marcin Gradowski
  • Kelly A. Servage
  • Krzysztof Pawłowski
  • Diana R. Tomchick
  • Vincent S. Tagliabracci
External organisations
  • University of Texas Southwestern Medical Center
  • Warsaw University of Life Sciences
  • Howard Hughes Medical Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Structural Biology
  • Medical Biotechnology
Original languageEnglish
Pages (from-to)787-792
Number of pages6
JournalScience (New York, N.Y.)
Issue number6442
Publication statusPublished - 2019
Publication categoryResearch