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Mycolyltransferase from Mycobacterium leprae Excludes Mycolate-containing Glycolipid Substrates.
- Source :
- Journal of Biochemistry; Nov2009, Vol. 146 Issue 5, p659-665, 7p, 1 Color Photograph, 2 Diagrams, 2 Graphs
- Publication Year :
- 2009
-
Abstract
- Trehalose dimycolate (TDM) is a major surface-exposed mycolyl glycolipid that contributes to the hydrophobic cell wall architecture of mycobacteria. Nevertheless, because of its potent adjuvant functions, pathogenic mycobacteria appear to have evolved an evasive maneuver to down-regulate TDM expression within the host. We have shown previously that Mycobacterium tuberculosis (M.tb) and Mycobacterium avium (M.av), replace TDM with glucose monomycolate (GMM) by borrowing host-derived glucose as an alternative substrate for the FbpA mycolyltransferase. Mycobacterium leprae (M.le), the causative microorganism of human leprosy, is also known to down-regulate TDM expression in infected tissues, but the function of its mycolyltransferases has been poorly analysed. We found that, unlike M.tb and M.av FbpA enzymes, M.av FbpA was unexpectedly inefficient in transferring α-branched mycolates, resulting in impaired production of both TDM and GMM. Molecular modelling and mutational analysis indicated that a bulky side chain of leucine at position 130 of M.le FbpA obstructed the intramolecular tunnel that was proposed to accommodate the α-branch portion of the substrates. Notably, even after a highly reductive evolution, M.le FbpA remained functional in terms of transferring unbranched acyl chains, suggesting a role that is distinct from that as a mycolyltransferase. [ABSTRACT FROM PUBLISHER]
- Subjects :
- GLYCOLIPIDS
GLUCOSE
MYCOBACTERIUM leprae
BACTERIAL cell walls
MYCOBACTERIA
Subjects
Details
- Language :
- English
- ISSN :
- 0021924X
- Volume :
- 146
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 47430127
- Full Text :
- https://doi.org/10.1093/jb/mvp113