Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 12, 2018
- Source ID
- 10.1073/pnas.1710741115
Entities
People
- Alexandre Hofer
- Alice E. Parnell
- Daniel Wohlwend
- Florian Kemper
- Henning J. Jessen
- Jennifer N Andexer
- Josh P. Prince
- Mariacarmela Giurrandino
- Nikola J. Schwarzer
- Oliver Einsle
- Peter L Roach
- Petra C. F. Oyston
- Silja Mordhorst
- Stefan Gerhardt
Organizations
- Defence Science and Technology Laboratory
- Defense Threat Reduction Agency
- Engineering and Physical Sciences Research Council
- German Research Foundation
- University of Freiburg
- University of Southampton
- University of Zurich