2PUN

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

2PUN の概要

• エントリーDOI: 10.2210/pdb2pun/pdb
• 関連するPDBエントリー: 2PU8 2PUI 2PUL
• 分子名称: Methylthioribose kinase, MAGNESIUM ION, 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE, ... (6 entities in total)
• 機能のキーワード: 5-methylthioribose kinase, methionine recycling pathway, transferase
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92314.29

構造登録者

Ku, S.-Y. (登録日: 2007-05-09, 公開日: 2007-05-22, 最終更新日: 2024-02-21)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)