Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria
| Autor: | Michael Proudfoot, Alexander F. Yakunin, Elena Evdokimova, Samvel Kochinyan, Andrzej Joachimiak, Alexei Savchenko, Greg Brown, Aled M. Edwards, Jerzy Osipiuk, Boguslaw Nocek |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular AMP phosphorylation Molecular Sequence Data Biology Crystallography X-Ray Catalysis Protein Structure Secondary Substrate Specificity chemistry.chemical_compound Adenosine Triphosphate Polyphosphates Catalytic Domain Amino Acid Sequence Multidisciplinary Alanine Phosphotransferases (Phosphate Group Acceptor) Kinase Polyphosphate Walker motifs Biological Sciences Protein Structure Tertiary Adenosine Diphosphate Adenosine diphosphate Kinetics Biochemistry chemistry Mutagenesis Pseudomonas aeruginosa Phosphorylation Energy source Adenosine triphosphate Sequence Alignment Sinorhizobium meliloti |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 105(46) |
| ISSN: | 1091-6490 |
| Popis: | Inorganic polyphosphate (polyP) is a linear polymer of tens or hundreds of phosphate residues linked by high-energy bonds. It is found in all organisms and has been proposed to serve as an energy source in a pre-ATP world. This ubiquitous and abundant biopolymer plays numerous and vital roles in metabolism and regulation in prokaryotes and eukaryotes, but the underlying molecular mechanisms for most activities of polyP remain unknown. In prokaryotes, the synthesis and utilization of polyP are catalyzed by 2 families of polyP kinases, PPK1 and PPK2, and polyphosphatases. Here, we present structural and functional characterization of the PPK2 family. Proteins with a single PPK2 domain catalyze polyP-dependent phosphorylation of ADP to ATP, whereas proteins containing 2 fused PPK2 domains phosphorylate AMP to ADP. Crystal structures of 2 representative proteins, SMc02148 from Sinorhizobium meliloti and PA3455 from Pseudomonas aeruginosa , revealed a 3-layer α/β/α sandwich fold with an α-helical lid similar to the structures of microbial thymidylate kinases, suggesting that these proteins share a common evolutionary origin and catalytic mechanism. Alanine replacement mutagenesis identified 9 conserved residues, which are required for activity and include the residues from both Walker A and B motifs and the lid. Thus, the PPK2s represent a molecular mechanism, which potentially allow bacteria to use polyP as an intracellular energy reserve for the generation of ATP and survival. |
| Databáze: | OpenAIRE |
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