Ppm1, a novel polyprenol monophosphomannose synthase from Mycobacterium tuberculosis
| Autor: | Alain R. Baulard, Walter Mühlecker, Camille Locht, Catherine E. Costello, Sudagar S Gurcha, Gurdyal S. Besra, Dean C. Crick, Patrick J. Brennan, D. Branch Moody, Laurent Kremer |
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| Rok vydání: | 2002 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Glycosylation Molecular Sequence Data Mannose Biochemistry Microbiology Mycobacterium tuberculosis chemistry.chemical_compound Polyprenol Biosynthesis Bacterial Proteins Amino Acid Sequence Cloning Molecular Molecular Biology DNA Primers Lipoarabinomannan Lipomannan biology ATP synthase Base Sequence Sequence Homology Amino Acid Cell Biology biology.organism_classification chemistry biology.protein Research Article |
| Zdroj: | The Biochemical journal. 365(Pt 2) |
| ISSN: | 0264-6021 |
| Popis: | Dolichol monophosphomannose (DPM) is an ever-present donor of mannose (Man) in various eukaryotic glycosylation processes. Intriguingly, the related polyprenol monophosphomannose (PPM) is involved in the biosynthesis of lipomannan and lipoarabinomanan, key bacterial factors termed modulins that are found in mycobacteria. Based on similarities to known DPM synthases, we have identified and characterized the PPM synthase of Mycobacterium tuberculosis, now termed Mt-Ppm1. In the present study, we demonstrate that Mt-Ppm1 possesses an unusual two-domain architecture, by which the second domain is sufficient for PPM synthesis. However, when overexpressed separately in mycobacteria, domain 1 of Mt-Ppm1 appears to increase the synthesis of PPM. Interestingly, other mycobacteria such as M. smegmatis, M. avium and M. leprae produce two distinct proteins, which are similar to the two domains found in Mt-Ppm1. Using an in vitro assay, we also demonstrate that Mt-Ppm1 transfers Man from GDP-Man to a structurally diverse range of lipid monophosphate acceptors. The identification of the PPM synthase as a key enzyme in lipoarabinomannan biosynthesis now provides an attractive candidate for gene disruption to generate mutants for subsequent immunological studies. PPM synthase can also be exploited as a target for specific inhibitors of M. tuberculosis. |
| Databáze: | OpenAIRE |
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