PDBsum entry: 2pun

Transferase

PDB id: 2pun

Contents

Protein chains

380 a.a. *

Ligands

CPS

ACP ×2

SR1 ×2

Metals

_MG ×2

Waters ×347

* Residue conservation analysis

PDB id:

2pun

Name:

Transferase

Title:

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

Structure:

Methylthioribose kinase. Chain: a, b. Synonym: mtr kinase. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Gene: mtnk, ykrt. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

2.30Å R-factor: 0.204 R-free: 0.255

Authors:

S.-Y.Ku

Key ref:

S.Y.Ku et al. (2007). Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding. J Biol Chem, 282, 22195-22206. PubMed id: 17522047 DOI: 10.1074/jbc.M611045200

Date:

09-May-07 Release date: 22-May-07

Protein chains

O31663  (MTNK_BACSU) -  Methylthioribose kinase

Seq: 397 a.a.

Struc: 380 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.100 - S-methyl-5-thioribose kinase.
• Reaction: ATP + S-methyl-5-thio-D-ribose = ADP + S-methyl-5-thio-alpha-D-ribose 1-phosphate

ATP + S-methyl-5-thio-D-ribose (Bound ligand (Het Group name = SR1) corresponds exactly) = ADP (Bound ligand (Het Group name = ACP) matches with 81.25% similarity) + S-methyl-5-thio-alpha-D-ribose 1-phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: response to stress (4 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1074/jbc.M611045200

J Biol Chem 282:22195-22206 (2007)

PubMed id: 17522047

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

S.Y.Ku, P.Yip, K.A.Cornell, M.K.Riscoe, J.B.Behr, G.Guillerm, P.L.Howell.

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.

Selected figure(s)

Figure 3.
FIGURE 3. Comparison of MTR kinase structures and active site. A, stereo ribbon presentation of C^ superimpositions of apo-MTR kinase and its ADP, AMPPCP, AMPPCP-MTR, and ADP-PO[4] complexes in gray, yellow, violet, purple, and red, respectively. B, stereo stick presentation of the active sites of the five MTR kinase structures. Panel B is colored as in A. The ligands and Mg(II) ions are shown as transparent stick and spheres, respectively, to show the residues behind. Residues that make hydrophobic interactions with the nucleotide or the substrate are labeled in brown. Note Leu^117 interacts with the nucleotide via its amino nitrogen and hence is labeled in black. While His^231 of the HGD motif does not interact with the substrates, it has been included for completeness and is labeled in gray.

Figure 7.
FIGURE 7. MTR binding site and the location of W- and G-loops. A, stereo view showing close up of the MTR binding site and relative positions of residue Trp^74 on the W-loop and Leu^345 and Leu^180. The [A] weighted F[o] - F[c] ligand omit map density for the substrate is shown and is contoured at 2.5 . B, stereo surface representation of MTR kinase in the same orientation as in Fig. 3A. The surface of monomer B of MTRK-AMPPCP-MTR complex is shown with AMPPCP-MTR in purple and ADP-PO[4] in red stick representation. The G-loop and the W-loop are shown in green. Trp^74 of the W-loop is disordered in this structure (see text).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 22195-22206) copyright 2007.

Figures were selected by an automated process.