結核菌糖脂質

We have accumulated knowledge of GPI biosynthesis in mammalian cells over years, and are now applying this knowledge for the understanding of GPI biosynthesis in pathogenic organisms. We are particularly interested in the biosynthesis of GPI in Trypanosoma brucei, and the biosynthesis of GPI-like glycolipids in mycobacteria. T. brucei is the causative agent of African sleeping sickness while mycobacteria cause a number of diseases including tuberculosis. These glycolipids are located to the cell surface of these pathogens, and play key roles in evasion from the hostﾕs immune attack. We thus consider the biosynthesis of these glycolipids as potential drug targets, and take multilateral approaches with primary focus on the comprehensive understanding of the GPI biosynthesis at molecular levels.

Four projects are currently underway:

(1) GPI transamidase, the enzyme that transfers complete GPI precursors onto nascent proteins, is a complex of at least 5 polypeptides. Catalytic mechanisms of this enzymatic machinery remain unclear in many aspects, and we aim to clarify the function of each component at molecular levels.

(2) Inositol residue of GPI is often acylated, but its physiological significance has remained speculative. We are currently trying to identify and characterize the genes involved in this enzymatic process hoping to clarify the importance of this phenomenon in the GPI metabolism.

(3) Trans-sialidase is an enzyme that transfers sialic acids onto GPI side chains. Sialic acid modification is essential for the survival of trypanosomes in the midgut of tsetse fly vector. Multiple homologues of this enzyme have been identified from the genome database, and thus we are currently trying to characterize the functions of each of these gene products.

(4) Phosphatidylinositol mannosides and lipoarabinomannan, immunologically important components of mycobacterial cell wall, are synthesized by metabolic pathways similar to eukaryotic GPI biosynthesis. We are trying to understand the biochemical and cell biological aspects of the biosynthesis of these glycolipids, including the identification of novel genes involved in these processes. Application of appropriate enzymes to the development of drug screening strategy is also underway.

Details of Trypanosoma Project (Under Construction)

Details of Mycobacteria Project (Under Construction)

Useful Links for Trypanosoma Research (Under Construction)

Useful Links for Mycobacterial Research (Under Construction)


	Glycolipid biosynthesis in pathogens and its application to drug development We have accumulated knowledge of GPI biosynthesis in mammalian cells over years, and are now applying this knowledge for the understanding of GPI biosynthesis in pathogenic organisms. We are particularly interested in the biosynthesis of GPI in Trypanosoma brucei, and the biosynthesis of GPI-like glycolipids in mycobacteria. T. brucei is the causative agent of African sleeping sickness while mycobacteria cause a number of diseases including tuberculosis. These glycolipids are located to the cell surface of these pathogens, and play key roles in evasion from the hostﾕs immune attack. We thus consider the biosynthesis of these glycolipids as potential drug targets, and take multilateral approaches with primary focus on the comprehensive understanding of the GPI biosynthesis at molecular levels. Four projects are currently underway: (1) GPI transamidase, the enzyme that transfers complete GPI precursors onto nascent proteins, is a complex of at least 5 polypeptides. Catalytic mechanisms of this enzymatic machinery remain unclear in many aspects, and we aim to clarify the function of each component at molecular levels. (2) Inositol residue of GPI is often acylated, but its physiological significance has remained speculative. We are currently trying to identify and characterize the genes involved in this enzymatic process hoping to clarify the importance of this phenomenon in the GPI metabolism. (3) Trans-sialidase is an enzyme that transfers sialic acids onto GPI side chains. Sialic acid modification is essential for the survival of trypanosomes in the midgut of tsetse fly vector. Multiple homologues of this enzyme have been identified from the genome database, and thus we are currently trying to characterize the functions of each of these gene products. (4) Phosphatidylinositol mannosides and lipoarabinomannan, immunologically important components of mycobacterial cell wall, are synthesized by metabolic pathways similar to eukaryotic GPI biosynthesis. We are trying to understand the biochemical and cell biological aspects of the biosynthesis of these glycolipids, including the identification of novel genes involved in these processes. Application of appropriate enzymes to the development of drug screening strategy is also underway. Details of Trypanosoma Project (Under Construction) Details of Mycobacteria Project (Under Construction) Useful Links for Trypanosoma Research (Under Construction) Useful Links for Mycobacterial Research (Under Construction)
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