2pul

From Proteopedia

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

Overview

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.

About this Structure

2PUL is a Single protein structure of sequence from Bacillus subtilis with MG, CPS and ACP as ligands. Active as S-methyl-5-thioribose kinase, with EC number 2.7.1.100 Full crystallographic information is available from OCA.

Reference

Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding., Ku SY, Yip P, Cornell KA, Riscoe MK, Behr JB, Guillerm G, Howell PL, J Biol Chem. 2007 Jul 27;282(30):22195-206. Epub 2007 May 23. PMID:17522047

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