2PUL

Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding

Summary for 2PUL

• Entry DOI: 10.2210/pdb2pul/pdb
• Related: 2PU8 2PUI 2PUN 2PUP
• Descriptor: Methylthioribose kinase, MAGNESIUM ION, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE, ... (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: 91953.85

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

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: 17522047
DOI: 10.1074/jbc.M611045200

Experimental method

X-RAY DIFFRACTION (2 Å)