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Structure of the YibK methyltransferase from Haemophilus influenzae (HI0766): A cofactor bound at a site formed by a knot

Authors

  • Kap Lim,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
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  • Hong Zhang,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
    Current affiliation:
    1. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas.
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  • Aleksandra Tempczyk,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
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  • Wojciech Krajewski,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
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  • Nicklas Bonander,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
    2. The National Institute of Standards and Technology, Gaithersburg, Maryland
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  • John Toedt,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
    Current affiliation:
    1. Department of Physical Science, Eastern Connecticut State University, Willimantic, Connecticut.
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  • Andrew Howard,

    1. Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois<
    2. Biological, Chemical, and Physical Science Department, Illinois Institute of Technology, Chicago, Illinois
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  • Edward Eisenstein,

    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
    2. The National Institute of Standards and Technology, Gaithersburg, Maryland
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  • Osnat Herzberg

    Corresponding author
    1. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland
    • Center for Advanced Research in Biotechnology, 9600 Gudelsky Drive, Rockville, MD 20850
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Abstract

The crystal structures of YibK from Haemophilus influenzae (HI0766) have been determined with and without bound cofactor product S-adenosylhomocysteine (AdoHcy) at 1.7 and 2.0 Å resolution, respectively. The molecule adopts an α/β fold, with a topology that differs from that of the classical methyltransferases. Most notably, HI0766 contains a striking knot that forms the binding crevice for the cofactor. The knot formation is correlated with an alternative arrangement of the secondary structure units compared with the classical methyltransferases. Two loop regions undergo conformational changes upon AdoHcy binding. In contrast to the extended conformation of the cofactor seen in the classical methyltransferase structures, AdoHcy binds to HI0766 in a bent conformation. HI0766 and its close sequence relatives are all shorter versions of the more remotely related rRNA/tRNA methyltransferases of the spoU sequence family. We propose that the spoU sequence family contains the same core domain for cofactor binding as HI0766 but has an additional domain for substrate binding. The substrate-binding domain is absent in HI0766 sequence family and may be provided by another Haemophilus influenzae partner protein, which is yet to be identified. Proteins 2003;51:56–67. © 2003 Wiley-Liss, Inc.

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