Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan
| Autor: | Delphi Chatterjee, Dean C. Crick, James C. Starbuck, Patrick J. Brennan, Stefan Berg, Varalakshmi D. Vissa, Jordi B. Torrelles |
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| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Chromatography Gas Proline Protein Conformation Amino Acid Motifs Molecular Sequence Data Mycobacterium smegmatis Carbohydrates Biochemistry Methylation Conserved sequence Protein structure Bacterial Proteins Arabinogalactan Glycosyltransferase Amino Acid Sequence Molecular Biology Conserved Sequence chemistry.chemical_classification Lipoarabinomannan Lipomannan biology Base Sequence Bacterial polysaccharide Glycosyltransferases Cell Biology Amino acid chemistry Genes Bacterial Mutation biology.protein Sequence Analysis |
| Zdroj: | The Journal of biological chemistry. 280(7) |
| ISSN: | 0021-9258 |
| Popis: | D-Arabinans, composed of D-arabinofuranose (D-Araf), dominate the structure of mycobacterial cell walls in two settings, as part of lipoarabinomannan (LAM) and arabinogalactan, each with markedly different structures and functions. Little is known of the complexity of their biosynthesis. beta-D-Arabinofuranosyl-1-monophosphoryldecaprenol is the only known sugar donor. EmbA, EmbB, and EmbC, products of the paralogous genes embA, embB, and embC, the sites of resistance to the anti-tuberculosis drug ethambutol (EMB), are the only known implicated enzymes. EmbA and -B apparently contribute to the synthesis of arabinogalactan, whereas EmbC is reserved for the synthesis of LAM. The Emb proteins show no overall similarity to any known proteins beyond Mycobacterium and related genera. However, functional motifs, equivalent to a proline-rich motif of several bacterial polysaccharide co-polymerases and a superfamily of glycosyltransferases, were found. Site-directed mutagenesis in glycosyltransferase superfamily C resulted in complete ablation of LAM synthesis. Point mutations in three amino acids of the proline motif of EmbC resulted in marked reduction of LAM-arabinan synthesis and accumulation of an unknown intermediate and of the known precursor lipomannan. Yet the pattern of the differently linked d-Araf units observed in wild type LAM-arabinan was largely retained in the proline motif mutants. The results allow for the presentation of a unique model of arabinan synthesis. |
| Databáze: | OpenAIRE |
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