2PUI
Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding
Summary for 2PUI
| Entry DOI | 10.2210/pdb2pui/pdb |
| Related | 2PU8 2PUL 2PUN 2PUP |
| Descriptor | Methylthioribose kinase, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | 5-methylthioribose kinase, methionine recycling pathway, transferase |
| Biological source | Bacillus subtilis |
| Total number of polymer chains | 2 |
| Total formula weight | 91846.44 |
| Authors | Ku, S.-Y. (deposition date: 2007-05-09, release date: 2007-05-22, Last modification date: 2024-02-21) |
| Primary citation | Ku, S.-Y.,Yip, P.,Cornell, K.A.,Riscoe, M.K.,Behr, J.-B.,Guillerm, G.,Howell, P.L. Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding J.Biol.Chem., 282:22195-22206, 2007 Cited by PubMed Abstract: 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-PO(4), 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(250)-Glu(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(233) of the catalytic HGD motif, a novel twin arginine motif (Arg(340)/Arg(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 ribosyl 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. PubMed: 17522047DOI: 10.1074/jbc.M611045200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
Download full validation report
