RRC ID 5750
Author Nakao H, Matsunaga I, Morita D, Aboshi T, Harada T, Nakagawa Y, Mori N, Sugita M.
Title Mycolyltransferase from Mycobacterium leprae excludes mycolate-containing glycolipid substrates.
Journal J. Biochem.
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 alpha-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 alpha-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.
Volume 146(5)
Pages 659-65
Published 2009-11
DOI 10.1093/jb/mvp113
PII mvp113
PMID 19628675
MeSH Acyltransferases / metabolism* Amino Acid Sequence Amino Acid Substitution / genetics Bacterial Proteins / chemistry Bacterial Proteins / metabolism Fatty Acids / metabolism Glycolipids / metabolism* Kinetics Leucine / metabolism Molecular Sequence Data Mutant Proteins / metabolism Mycobacterium leprae / enzymology* Mycolic Acids / metabolism* Protein Binding Substrate Specificity
IF 2.23
Times Cited 4
General Microbes JCM9386