Abstract:
:Infective stages of the protozoan parasite Leishmania spp. accumulate a class of beta-1,2-mannan oligosaccharides as their major carbohydrate reserve material. Here, we describe the biosynthesis of Leishmania mannan. Mannan precursors were identified by metabolic labeling of Leishmania mexicana promastigotes with [(3)H]mannose. Label was initially incorporated into a phosphomannose primer and short phosphorylated beta-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-alpha-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 transferases in 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Sernee MF,Ralton JE,Dinev Z,Khairallah GN,O'Hair RA,Williams SJ,McConville MJdoi
10.1073/pnas.0603539103subject
Has Abstractpub_date
2006-06-20 00:00:00pages
9458-63issue
25eissn
0027-8424issn
1091-6490pii
0603539103journal_volume
103pub_type
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