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Mechanistic Studies of an IspH-Catalyzed Reaction: Implications for Substrate Binding and Protonation in the Biosynthesis of Isoprenoids

Authors

  • Wei-chen Chang,

    1. Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712 (USA)
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    • These authors contributed equally to this work.

  • Dr. Youli Xiao,

    1. Department of Chemistry, Boston University, Boston, MA 02215 (USA)
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    • These authors contributed equally to this work.

  • Prof. Dr. Hung-wen Liu,

    Corresponding author
    1. Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712 (USA)
    • Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712 (USA)
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  • Prof. Dr. Pinghua Liu

    Corresponding author
    1. Department of Chemistry, Boston University, Boston, MA 02215 (USA)
    • Department of Chemistry, Boston University, Boston, MA 02215 (USA)
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  • Financial support for this work was provided in part by grants from the National Science Foundation (CAREER, CHE-0748504 to P.L.), the National Institutes of Health (GM 093903 to P.L.), and the Welch Foundation (F-1511 to H.-w.L.).

Abstract

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Angriffspunkt erkannt: Mechanistische Studien der IspH-katalysierten reduktiven Dehydroxylierung von 4-Hydroxy-3-methyl-2-(E)-1-diphosphat (HMBPP) zu Isopentenyldiphosphat und Dimethylallyldiphosphat ergeben, dass sowohl die 4-OH-Gruppe als auch die Doppelbindung von HMBPP zur Bildung des Substrat-IspH-Komplexes beitragen können. Markierungsstudien sprechen der 4-OH-Gruppe des Substrats nun die Hauptrolle beim Positionieren im aktiven Zentrum des Enzyms zu.

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