| Biosynthesis of the linkage region of the mycobacterial cell wall. | |
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MedLine Citation:
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PMID: 8631826 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The "core" structure of the cell wall of Mycobacterium and related genera is unique among prokaryotes, consisting of a covalently linked complex of mycolic acids, D-arabinan and D-galactan (mycolylarabinogalactan, mAG), which, in turn, is linked to peptidoglycan via a special linkage unit, -alpha-L-Rhap(1-->3)-D-GlcNAc-P-. Little is known of the biosynthesis of this complex, although it is the site of action of several common anti-tuberculosis drugs. Isolated cell membranes of Mycobacterium smegmatis catalyzed the incorporation of [14C]GlcNAc from UDP-[14C]GlcNAc into two glycolipids (1 and 2) and of [14C]Rha from TDP-[14C]Rha into glycolipid 2. These products were characterized as polyprenol-P-P-GlcNAc (glycolipid 1) and polyprenol-P-P-GlcNAc-Rha (glycolipid 2) based on sensitivity of synthesis to tunicamycin, chromatographic characterization of the products of mild acid hydrolysis, and mass spectral analysis of the glycosyl and polyprenyl units. Glycolipids 1 and 2 were shown to be precursors of the linkage unit in polymerized cell wall. The inclusion in the assays of UDP-[14C]Galp and a preparation of cell walls allowed the incorporation of [14C]Gal into two further glycolipids (3 and 4). Preliminary evidence indicates a precursor-product relationship among glycolipids 1, 2, 3, and 4. Thus, the first steps in the biosynthesis of the mycobacterial cell wall involve synthesis of the linkage disaccharide on a polyprenyl-P-P carrier followed by growth of the galactan unit. Assays are thus defined for the screening of new anti-tuberculosis drugs active against cell wall synthesis. |
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Authors:
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K Mikusová; M Mikus; G S Besra; I Hancock; P J Brennan |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 271 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1996 Mar |
Date Detail:
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Created Date: 1996-07-03 Completed Date: 1996-07-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 7820-8 Citation Subset: IM |
Affiliation:
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Department of Microbiology, Colorado State University, Fort Collins, 80523, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Carbohydrate Conformation Carbohydrate Sequence Carbon Radioisotopes Cell Wall / metabolism Chromatography, Thin Layer Galactose / metabolism Kinetics Lipopolysaccharides / biosynthesis*, chemistry, isolation & purification Models, Molecular Molecular Sequence Data Mycobacterium / metabolism* Oligosaccharides / biosynthesis, chemistry, isolation & purification Uridine Diphosphate N-Acetylglucosamine / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI 18357/AI/NIAID NIH HHS; AI 30189/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carbon Radioisotopes; 0/Lipopolysaccharides; 0/Oligosaccharides; 26566-61-0/Galactose; 528-04-1/Uridine Diphosphate N-Acetylglucosamine |
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