1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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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
Research Article
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Cite this article as: eLife 2015;4:e07607 doi: 10.7554/eLife.07607

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.

Reviewing Editor

  1. Ben Cravatt, The Scripps Research Institute, United States

Publication history

  1. Received: March 21, 2015
  2. Accepted: July 29, 2015
  3. Accepted Manuscript published: July 30, 2015 (version 1)
  4. Version of Record published: August 27, 2015 (version 2)

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.

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