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O-Glycoside Orientation Is an Essential Aspect of Base J Recognition by the Kinetoplastid DNA-Binding Protein JBP1

Authors

  • Rajesh K. Grover Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-7835
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  • Stephanie J. K. Pond Dr.,

    1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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  • Qizhi Cui Dr.,

    1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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  • Prem Subramaniam Dr.,

    1. Department of Infectology, Scripps Research Institute—Florida, 5353 Parkside Drive RF-2, Jupiter, FL 33458, USA
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  • David A. Case Prof.,

    1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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  • David P. Millar Prof.,

    1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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  • Paul Wentworth Jr. Prof.

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-7835
    2. The Scripps-Oxford Laboratory, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
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  • This work was supported by the Skaggs Institute for Chemical Biology (P.W.). We thank Dr. P. Ordoukhanian of the TSRI Nucleic Acid Core and E. J. C. van der Schans for oligonucleotide synthesis and purification. P.W. and R.K.G. thank M. Puga for assistance during the synthesis of 1 ah. P.S. thanks Prof. C. Weissmann for his assistance and support.

Abstract

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Ein empfindliches Protein: Der Vergleich der Dissoziationskonstanten und Moleküldynamikschnappschüsse einer Reihe synthetischer telomerer doppelsträngiger DNA-Sequenzen mit HMdU-O-Glycosiden ergab, dass das DNA-bindende Protein von Kinetoplastiden wie Leishmania und Trypanosoma, JBP1, eine kritische Edge-on-Konformation des Pyranosylrings von Base J erkennt. Wenn diese Konformation gestört ist, nimmt die JBP1-Bindung drastisch ab.

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