Cover Picture: Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis (ChemBioChem 16/2013)

Authors

  • Dr. Jacob L. Houghton,

    1. Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109 (USA)
    2. Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 (USA)
    Search for more papers by this author
    • These two authors contributed equally to this work.

  • Dr. Tapan Biswas,

    1. Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109 (USA)
    Search for more papers by this author
    • These two authors contributed equally to this work.

  • Dr. Wenjing Chen,

    1. Chemical Biology Doctoral Program, University of Michigan, Ann Arbor, MI 48109 (USA)
    2. Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 (USA)
    Search for more papers by this author
  • Dr. Oleg V. Tsodikov,

    Corresponding author
    1. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536-0596 (USA)
    • Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536-0596 (USA)

    Search for more papers by this author
  • Dr. Sylvie Garneau-Tsodikova

    Corresponding author
    1. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536-0596 (USA)
    • Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536-0596 (USA)

    Search for more papers by this author

Abstract

original image

The cover picture shows how the Eis enzyme from Mycobacterium tuberculosis binds its substrate, aminoglycoside tobramycin, for acetylation. Acetylation of aminoglycosides by Eis causes resistance to these drugs in tuberculosis. On p. 2127 ff., O. V. Tsodikov, S. Garneau-Tsodikova et al. reveal two new acetylation positions for this enzyme on aminoglycoside scaffolds: the 3′′-amine of tobramycin, kanamycin, and amikacin as well as the γ-amine of the 4-amino-2-hydroxybutyryl group of amikacin. A cartoon of the crystal structure of the ternary complex of Eis, CoA, and tobramycin demonstrates that this aminoglycoside can bind Eis in two distinct conformations, one for acetylation of the 6′-position (tobramycin in pink with the acetylation position in turquoise) and one for acetylation at the 3′′-position (tobramycin in green with the acetylation position in lilac).

Cartoon 1.

Ancillary