Structures of 5-Methylthioribose Kinase Reveal Substrate Specificity and Unusual Mode of Nucleotide Binding
| Autor: | Shao Yang Ku, Jean-Bernard Behr, P. Lynne Howell, Kenneth A. Cornell, Patrick Yip, Georges Guillerm, Michael K. Riscoe |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation Ribose Bacillus subtilis Biochemistry Substrate Specificity Structure-Activity Relationship chemistry.chemical_compound Methionine Bacterial Proteins Transferase Nucleotide Protein kinase A Molecular Biology Binding selectivity chemistry.chemical_classification Binding Sites biology Adenine Nucleotides Kinase Cell Biology biology.organism_classification Phosphotransferases (Alcohol Group Acceptor) Enzyme chemistry |
| Zdroj: | Journal of Biological Chemistry. 282:22195-22206 |
| ISSN: | 0021-9258 |
| Popis: | The methionine salvage pathway is ubiquitous in all organisms, but metabolic variations exist between bacteria and mammals. 5-Methylthioribose (MTR) kinase is a key enzyme in methionine salvage in bacteria and the absence of a mammalian homolog suggests that it is a good target for the design of novel antibiotics. The structures of the apo-form of Bacillus subtilis MTR kinase, as well as its ADP, ADP-PO4, AMPPCP, and AMPPCP-MTR complexes have been determined. MTR kinase has a bilobal eukaryotic protein kinase fold but exhibits a number of unique features. The protein lacks the DFG motif typically found at the beginning of the activation loop and instead coordinates magnesium via a DXE motif (Asp{sup 250}-Glu{sup 252}). In addition, the glycine-rich loop of the protein, analogous to the 'Gly triad' in protein kinases, does not interact extensively with the nucleotide. The MTR substrate-binding site consists of Asp{sup 233} of the catalytic HGD motif, a novel twin arginine motif (Arg{sup 340}/Arg{sup 341}), and a semi-conserved W-loop, which appears to regulate MTR binding specificity. No lobe closure is observed for MTR kinase upon substrate binding. This is probably because the enzyme lacks the lobe closure/inducing interactions between the C-lobe of the protein and the ribosylmore » moiety of the nucleotide that are typically responsible for lobe closure in protein kinases. The current structures suggest that MTR kinase has a dissociative mechanism.« less |
| Databáze: | OpenAIRE |
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