Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis
- 18 July 2004
- journal article
- research article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 11 (8) , 721-729
- https://doi.org/10.1038/nsmb802
Abstract
Sulfolipid-1 (SL-1) is an abundant sulfated glycolipid and potential virulence factor found in Mycobacterium tuberculosis. SL-1 consists of a trehalose-2-sulfate (T2S) disaccharide elaborated with four lipids. We identified and characterized a conserved mycobacterial sulfotransferase, Stf0, which generates the T2S moiety of SL-1. Biochemical studies demonstrated that the enzyme requires unmodified trehalose as substrate and is sensitive to small structural perturbations of the disaccharide. Disruption of stf0 in Mycobacterium smegmatis and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively. The structure of Stf0 at a resolution of 2.6 Å reveals the molecular basis of trehalose recognition and a unique dimer configuration that encloses the substrate into a bipartite active site. These data provide strong evidence that Stf0 carries out the first committed step in the biosynthesis of SL-1 and establish a system for probing the role of SL-1 in M. tuberculosis infection.Keywords
This publication has 68 references indexed in Scilit:
- Comparison of Antibody Responses to a Potential Combination of Specific Glycolipids and Proteins for Test Sensitivity Improvement in Tuberculosis SerodiagnosisClinical and Vaccine Immunology, 2004
- Screening and Identification of Acidic Carbohydrates in Bovine Colostrum by Using Ion/Molecule Reactions and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: Specificity toward Phosphorylated ComplexesAnalytical Chemistry, 2003
- Use of TLS parameters to model anisotropic displacements in macromolecular refinementActa Crystallographica Section D-Biological Crystallography, 2001
- Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequenceNature, 1998
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa Crystallographica Section D-Biological Crystallography, 1997
- [20] Processing of X-ray diffraction data collected in oscillation modePublished by Elsevier ,1997
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994
- Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and RapamycinJournal of Molecular Biology, 1993
- Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv II. Structural studiesBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1970
- Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv I. Purification and propertiesBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1970