title: 5-Methylthiopentose: a new substituent on lipoarabinomannan in Mycobacterium tuberculosis.
abstract: We have identified and characterised in several strains of Mycobacterium tuberculosis a new 5-methylthiopentose substituent on lipoarabinomannan (LAM). The 5-methylthiopentose was initially observed in heteronuclear (1)H-(13)C-NMR spectra of intact, (13)C-enriched LAM. Oligosaccharides carrying this substituent were released from (13)C-enriched LAM and from unlabelled LAM using an endo-arabinanase from Cellulomonas gellida. The presence of the methylthio group in these oligosaccharides was established using NMR, high-resolution Fourier-transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry using a Q-TOF mass spectrometer. The 5-methylthiopentose is linked to a terminal mannose in the cap structures of these oligosaccharides as evidenced by tandem mass spectrometry and by NMR. We suggest interference with the signal transduction mechanisms of infected macrophages as a possible function for this newly discovered LAM substituent.
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Achim
authors.initials: A
authors.lastname: Treumann
authors.forename: Feng
authors.initials: F
authors.lastname: Xidong
authors.forename: Liam
authors.initials: L
authors.lastname: McDonnell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Derrick
authors.forename: Alison E
authors.initials: AE
authors.lastname: Ashcroft
authors.forename: Delphi
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Steve W
authors.initials: SW
authors.lastname: Homans
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006026:Glycoside Hydrolases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000378:metabolism; D008361:Mannosidases / Q000378:metabolism; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D013865:Thioglycosides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D043323:alpha-Mannosidase
chemical_list: C448900:5-methylthiopentose; D008070:Lipopolysaccharides; D013865:Thioglycosides; C050016:lipoarabinomannan; D006026:Glycoside Hydrolases; D008361:Mannosidases; D043323:alpha-Mannosidase; D008358:Mannose