The enterrococcal cytolysin synthetase has an unanticipated lipid kinase fold

  1. Shi-Hui Dong
  2. Weixin Tang
  3. Tiit Lukk
  4. Yi Yu
  5. Satish K Nair
  6. Wilfred A van der Donk  Is a corresponding author
  1. University of Illinois at Urbana-Champaign, United States
  2. Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, United States
  3. Cornell High Energy Synchrotron Source, United States
  4. University of Illinois at Urbana-Champaign, United Kingdom

Abstract

The enterococcal cytolysin is a virulence factor consisting of two post-translationally modified peptides that synergistically kill human immune cells. Both peptides are made by CylM, a member of the LanM lanthipeptide synthetases. CylM catalyzes seven dehydrations of Ser and Thr residues and three cyclization reactions during the biosynthesis of the cytolysin large subunit. We present here the 2.2 Å resolution structure of CylM, the first structural information on a LanM. Unexpectedly, the structure reveals that the dehydratase domain of CylM resembles the catalytic core of eukaryotic lipid kinases, despite the absence of sequence homology. The kinase and phosphate elimination active sites that effect net dehydration are immediately adjacent to each other. Characterization of mutants provided insights into the mechanism of the dehydration process. The structure is also of interest because of the interactions of human homologs of lanthipeptide cyclases with kinases such as mammalian target of rapamycin (mTOR).

Article and author information

Author details

  1. Shi-Hui Dong

    Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  2. Weixin Tang

    Roger Adams Laboratory, Department of Chemistry, Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  3. Tiit Lukk

    Cornell High Energy Synchrotron Source, Ithaca, United States
    Competing interests
    No competing interests declared.
  4. Yi Yu

    Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United Kingdom
    Competing interests
    No competing interests declared.
  5. Satish K Nair

    Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  6. Wilfred A van der Donk

    Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    For correspondence
    vddonk@illinois.edu
    Competing interests
    Wilfred A van der Donk, Reviewing editor, eLife.

Copyright

© 2015, Dong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,189
    views
  • 638
    downloads
  • 86
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shi-Hui Dong
  2. Weixin Tang
  3. Tiit Lukk
  4. Yi Yu
  5. Satish K Nair
  6. Wilfred A van der Donk
(2015)
The enterrococcal cytolysin synthetase has an unanticipated lipid kinase fold
eLife 4:e07607.
https://doi.org/10.7554/eLife.07607

Share this article

https://doi.org/10.7554/eLife.07607