Open AccessLeishmania β-1,2-mannan is assembled on a mannose-cyclic phosphate primer
Author(s) -
M. Fleur Sernee,
Julie E. Ralton,
Zoran Dinev,
George N. Khairallah,
Richard A. J. O’Hair,
Spencer J. Williams,
Malcolm J. McConville
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0603539103
Subject(s) - mannan , mannose , chemistry , primer (cosmetics) , biochemistry , mannan binding lectin , leishmania , lectin , polysaccharide , parasite hosting , computer science , world wide web , organic chemistry
Infective stages of the protozoan parasiteLeishmania spp. accumulate a class of β-1,2-mannan oligosaccharides as their major carbohydrate reserve material. Here, we describe the biosynthesis ofLeishmania mannan. Mannan precursors were identified by metabolic labeling ofLeishmania mexicana promastigotes with [3 H]mannose. Label was initially incorporated into a phosphomannose primer and short phosphorylated β-1,2-mannan oligomers that were two to five residues long. Analysis of the mannan primer by Fourier transform ion-cyclotron resonance MS and various enzymatic and chemical treatments and comparison with authentic mannose (Man) phosphates indicated the presence of Man-α-1,4-cyclic phosphate. This primer was synthesized from Man-6-phosphate by means of Man-1-phosphate in a cell-free system. Short mannan chains containing the primer were subsequently dephosphorylated and then further elongated by GDP-Man-dependent transferasesin vivo and in the cell-free system. The synthesis of this glycan primer likely constitutes a key regulatory step in mannan biosynthesis and is a potential target for antileishmanial drugs.