The Active Site of an Enzyme Can Host Both Enantiomers of a Racemic Ligand Simultaneously

Authors

  • Matthias Mentel Dr.,

    1. Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany)
    2. Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
    3. European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg (Germany)
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  • Wulf Blankenfeldt Dr.,

    1. Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany), Fax: (+49) 231-133-2399
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  • Rolf Breinbauer Prof. Dr.

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 16, 8010 Graz (Austria), Fax: (+43) 316-873-8740
    2. Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany)
    3. Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany)
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  • This work was supported by the Max Planck Society, the Bioband of TU Dortmund (R.B. and W.B.), the Deutsche Forschungsgemeinschaft (grant BL587 to W.B.), and the University of Leipzig (R.B.). W.B. thanks Roger S. Goody for his support. We thank Dmitri V. Mavrodi and Linda S. Thomashow for the expression plasmid and Isha Himani Jain for performing crystallization experiments. The help of the X-ray communities at the MPI of Molecular Physiology, the MPI for Medical Research, and the beamline staff at beamline X10SA of the Swiss Light Source with data collection is gratefully acknowledged.

Abstract

original image

Two in one: Proteins usually bind only one enantiomer of a racemic ligand. Now a new binding mode for chiral drugs has been identified by protein crystallography. The homodimeric enzyme PhzA/B (in the picture the monomers are yellow and magenta) can host both enantiomers of a racemic ligand (light and dark gray) in its active site at the same time (dark red Br, blue N, light red O).

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