Taxonomic group: bacteria / Actinobacteria
(Phylum: Actinobacteria)
Associated disease: tuberculosis [ICD11:
XN1N2 
]
NCBI PubMed ID: 23536839Publication DOI: 10.1371/journal.pone.0058954Journal NLM ID: 101285081Publisher: San Francisco, CA: Public Library of Science
Correspondence: Chalut C <christian.chalut
ipbs.fr>
Institutions: Centre national de la recherche scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France, Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France
Phenolic glycolipids are produced by a very limited number of slow-growing mycobacterial species, most of which are pathogen for humans. In Mycobacterium tuberculosis, the etiologic agent of tuberculosis, these molecules play a role in the pathogenicity by modulating the host immune response during infection. The major variant of phenolic glycolipids produced by M. tuberculosis, named PGL-tb, consists of a large lipid core terminated by a glycosylated aromatic nucleus. The carbohydrate part is composed of three sugar residues, two rhamnosyl units and a terminal fucosyl residue, which is per-O-methylated, and seems to be important for pathogenicity. While most of the genes responsible for the synthesis of the lipid core domain and the saccharide appendage of PGL-tb have been characterized, the enzymes involved in the O-methylation of the fucosyl residue of PGL-tb remain unknown. In this study we report the identification and characterization of the methyltransferases required for the O-methylation of the terminal fucosyl residue of PGL-tb. These enzymes are encoded by genes Rv2954c, Rv2955c and Rv2956. Mutants of M. tuberculosis harboring deletion within these genes were constructed. Purification and analysis of the phenolglycolipids produced by these strains, using a combination of mass spectrometry and NMR spectroscopy, revealed that Rv2954c, Rv2955c and Rv2956 encode the methyltransferases that respectively catalysed the O-methylation of the hydroxyl groups located at positions 3, 4 and 2 of the terminal fucosyl residue of PGL-tb. Our data also suggest that methylation at these positions is a sequential process, starting with position 2, followed by positions 4 and 3
gene, virulence, complex, identification, methylation, transposon mutagenesis, strains, smegmatis, bcg
Structure type: oligomer
Location inside paper: fig. 5, product C
Compound class: glycoconjugate
Contained glycoepitopes: IEDB_136045,IEDB_136105,IEDB_142489,IEDB_144562,IEDB_152214,IEDB_174333,IEDB_225177,IEDB_885823,SB_86
Methods: 13C NMR, 1H NMR, MALDI-TOF MS, MS
Enzymes that release or process the structure: Rv2955
Comments, role: The number of atoms is varied from 15 to 17 in the backbone before the side chain and from 18 to 22 in the side chain. This structure has lower mobility than PGL-tb.
Related record ID(s): 45303, 45304, 45305, 45306, 45308, 45309, 45310
NCBI Taxonomy refs (TaxIDs): 83332
Show glycosyltransferases
NMR conditions: in CDCl3
[as TSV]
13C NMR data:
missing...
1H NMR data:
Linkage Residue H1 H2 H3 H4 H5 H6
1,3,3,2 Me
1,3,3,3 Me
1,3,3 aLFucp 5.15 3.58 3.64 3.93 4.10 1.32
1,3 aLRhap 5.14 4.12 3.81 3.66 3.95 1.36
1,2 Me
1 aLRhap 5.51 3.75 4.05 3.68 3.78 1.29
Subst
1H NMR data:
| Linkage | Residue | H1 | H2 | H3 | H4 | H5 | H6 |
|---|
| 1,3,3,2 | Me | |
| 1,3,3,3 | Me | |
| 1,3,3 | aLFucp | 5.15 | 3.58 | 3.64 | 3.93 | 4.10 | 1.32 |
| 1,3 | aLRhap | 5.14 | 4.12 | 3.81 | 3.66 | 3.95 | 1.36 |
| 1,2 | Me | |
| 1 | aLRhap | 5.51 | 3.75 | 4.05 | 3.68 | 3.78 | 1.29 |
| | Subst | |
|
There is only one chemically distinct structure:
Found 
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