Crystal structure of a polyphosphate kinase and its implications for polyphosphate synthesis.
Polyphosphate (polyP), a linear polymer of hundreds of orthophosphate residues, exists in all tested cells in nature, from pathogenic bacteria to mammals. In bacteria, polyP has a crucial role in stress responses and stationary-phase survival. Polyphosphate kinase (PPK) is the principal enzyme that catalyses the synthesis of polyP in bacteria. It has been shown that PPK is required for bacterial motility, biofilm formation and the production of virulence factors. PPK inhibitors may thus provide a unique therapeutic opportunity against antibiotic-resistant pathogens. Here, we report crystal structures of full-length Escherichia coli PPK and its complex with AMPPNP (beta-gamma-imidoadenosine 5-phosphate). PPK forms an interlocked dimer, with each 80 kDa monomer containing four structural domains. The PPK active site is located in a tunnel, which contains a unique ATP-binding pocket and may accommodate the translocation of synthesized polyP. The PPK structure has laid the foundation for understanding the initiation of polyP synthesis by PPK.
Zhu
Ye
Y
Department of Biological Structure, Box 357420, University of Washington, Seattle, Washington 98195, USA.
Huang
Weijun
W
Lee
Sam S K
SS
Xu
Wenqing
W
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D003461:Crystallography; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism; D011122:Polyphosphates / Q000378:metabolism*; D011487:Protein Conformation
D029968:Escherichia coli Proteins; D011122:Polyphosphates; D000266:Adenylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C475691:polyphosphate kinase, E coli