A Comprehensive Study of the Interaction between Peptidoglycan Fragments and the Extracellular Domain of Mycobacterium tuberculosis Ser/Thr Kinase PknB

Qianqian Wang, Roberta Marchetti, Sladjana Prisic, Kentaro Ishii, Yohei Arai, Ippei Ohta, Shinsuke Inuki, Susumu Uchiyama, Alba Silipo, Antonio Molinaro, Robert N. Husson, Koichi Fukase, Yukari Fujimoto

研究成果: Article

4 引用 (Scopus)

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The Mycobacterium tuberculosis Ser/Thr kinase PknB is implicated in the regulation of bacterial cell growth and cell division. The intracellular kinase function of PknB is thought to be triggered by peptidoglycan (PGN) fragments that are recognized by the extracytoplasmic domain of PknB. The PGN in the cell wall of M. tuberculosis has several unusual modifications, including the presence of N-glycolyl groups (in addition to N-acetyl groups) in the muramic acid residues and amidation of d-Glu in the peptide chains. Using synthetic PGN fragments incorporating these diverse PGN structures, we analyzed their binding characters through biolayer interferometry (BLI), NMR spectroscopy, and native mass spectrometry (nMS) techniques. The results of BLI showed that muropeptides containing 1,6-anhydro-MurNAc and longer glycan chains exhibited higher binding potency and that the fourth amino acid of the peptide stem, d-Ala, was crucial for protein recognition. Saturation transfer difference (STD) NMR spectroscopy indicated the major involvement of the stem peptide region in the PASTA-PGN fragment binding. nMS suggested that the binding stoichiometry was 1:1. The data provide the first molecular basis for the specific interaction of PGN with PknB and firmly establish PGNs as the effective ligands of PknB.

元の言語English
ページ(範囲)2094-2098
ページ数5
ジャーナルChemBioChem
18
発行部数21
DOI
出版物ステータスPublished - 2017 11 2

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

これを引用

Wang, Q., Marchetti, R., Prisic, S., Ishii, K., Arai, Y., Ohta, I., Inuki, S., Uchiyama, S., Silipo, A., Molinaro, A., Husson, R. N., Fukase, K., & Fujimoto, Y. (2017). A Comprehensive Study of the Interaction between Peptidoglycan Fragments and the Extracellular Domain of Mycobacterium tuberculosis Ser/Thr Kinase PknB. ChemBioChem, 18(21), 2094-2098. https://doi.org/10.1002/cbic.201700385