Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
NCBI PubMed ID: 25361768Publication DOI: 10.1074/jbc.M114.616300Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: makotoi
agr.kyushu-u.ac.jp
Institutions: Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Japan, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Japan, Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Japan
Cryptococcosis is an infectious disease caused by pathogenic fungi, such as Cryptococcus neoformans and Cryptococcus gattii. The ceramide structure (methyl-d18:2/h18:0) of C. neoformans glucosylceramide (GlcCer) is characteristic and strongly related to its pathogenicity. We recently identified endoglycoceramidase-related protein 1 (EGCrP1) as a glucocerebrosidase in C. neoformans and showed that it was involved in the quality control of GlcCer by eliminating immature GlcCer during the synthesis of GlcCer (Ishibashi, Y., Ikeda, K., Sakaguchi, K., Okino, N., Taguchi, R., and Ito, M. (2012) Quality control of fungus-specific glucosylceramide in Cryptococcus neoformans by endoglycoceramidase-related protein 1 (EGCrP1). J. Biol. Chem. 287, 368-381). We herein identified and characterized EGCrP2, a homologue of EGCrP1, as the enzyme responsible for sterylglucoside catabolism in C. neoformans. In contrast to EGCrP1, which is specific to GlcCer, EGCrP2 hydrolyzed various β-glucosides, including GlcCer, cholesteryl-β-glucoside, ergosteryl-β-glucoside, sitosteryl-β-glucoside, and para-nitrophenyl-β-glucoside, but not α-glucosides or β-galactosides, under acidic conditions. Disruption of the EGCrP2 gene (egcrp2) resulted in the accumulation of a glycolipid, the structure of which was determined following purification to ergosteryl-3β-glucoside, a major sterylglucoside in fungi, by mass spectrometric and two-dimensional nuclear magnetic resonance analyses. This glycolipid accumulated in vacuoles and EGCrP2 was detected in vacuole-enriched fraction. These results indicated that EGCrP2 was involved in the catabolism of ergosteryl-β-glucoside in the vacuoles of C. neoformans. Distinct growth arrest, a dysfunction in cell budding, and an abnormal vacuole morphology were detected in the egcrp2-disrupted mutants, suggesting that EGCrP2 may be a promising target for anti-cryptococcal drugs. EGCrP2, classified into glycohydrolase family 5, is the first steryl-β-glucosidase identified as well as a missing link in sterylglucoside metabolism in fungi
metabolism, glycolipid, fungi, glycosidase, sterol
Structure type: monomer ; 766.5
Location inside paper: Fig. 10, B
Compound class: cerebroside
Contained glycoepitopes: IEDB_137339,IEDB_141817,IEDB_142488,IEDB_146664,IEDB_174031,IEDB_604755,IEDB_952460,IEDB_983931,SB_192,SB_5
Methods: 13C NMR, 1H NMR, gel filtration, NMR-2D, SDS-PAGE, DNA techniques, MALDI-TOF MS, biological assays, HPLC, Southern blotting, extraction, cell growth, protein detection, enzymatic assay, flow cytometry analysis, centrifugation
Enzymes that release or process the structure: glucocerebrosidase (EGCrP1), steryl-β-glucosidase (EGCrP2)
Related record ID(s): 48262, 48263, 48265, 48266
NCBI Taxonomy refs (TaxIDs): 235443
Show glycosyltransferases
There is only one chemically distinct structure:
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