Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures

  • Alice E. Parnell
    Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, United Kingdom;
  • Silja Mordhorst
    Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Florian Kemper
    Institute of Biochemistry, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Mariacarmela Giurrandino
    Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, United Kingdom;
  • Josh P. Prince
    Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, United Kingdom;
  • Nikola J. Schwarzer
    Institute of Biochemistry, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Alexandre Hofer
    Organic Chemistry Institute, University of Zürich, 8057 Zürich, Switzerland;
  • Daniel Wohlwend
    Institute of Biochemistry, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Henning J. Jessen
    Organic Chemistry Institute, University of Zürich, 8057 Zürich, Switzerland;
  • Stefan Gerhardt
    Institute of Biochemistry, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Oliver Einsle
    Institute of Biochemistry, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Petra C. F. Oyston
    Institute for Life Sciences, University of Southampton, Southampton, Hampshire SO17 1BJ, United Kingdom;
  • Jennifer N. Andexer
    Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
  • Peter L. Roach
    Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, United Kingdom;

書誌事項

公開日
2018-03-12
権利情報
  • http://www.pnas.org/site/aboutpnas/licenses.xhtml
DOI
  • 10.1073/pnas.1710741115
公開者
National Academy of Sciences

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説明

<jats:title>Significance</jats:title> <jats:p>Polyphosphate kinases (PPKs) are involved in many metabolic processes in bacteria, including pathogenic species. As these enzymes are not present in animals, they are a prime target for the development of novel antibiotics. The detailed knowledge of the mechanism of action and structure–function relationships of these enzymes is of utmost importance for the identification and design of new pharmaceutically active compounds and the rational improvement of lead structures. In addition, PPKs use inexpensive and stable polyphosphate as a phosphate donor and phosphorylate nucleoside 5′-mono- as well as 5′-diphosphates. This makes them of special interest for application in ATP regeneration systems, which can be efficiently coupled to ATP-consuming enzymes in environmentally friendly and sustainable biotechnological processes.</jats:p>

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