Abstract:
:Glycosyl hydrolases (GHs) are carbohydrate-active enzymes that hydrolyze a specific β-glycosidic bond in glycoconjugate substrates; β-glucosidases degrade glucosylceramide, a ubiquitous glycosphingolipid. GHs are grouped into structurally similar families that themselves can be grouped into clans. GH1, GH5, and GH30 glycosidases belong to clan A hydrolases with a catalytic (β/α)8 TIM barrel domain, whereas GH116 belongs to clan O with a catalytic (α/α)6 domain. In humans, GH abnormalities underlie metabolic diseases. The lysosomal enzyme glucocerebrosidase (family GH30), deficient in Gaucher disease and implicated in Parkinson disease etiology, and the cytosol-facing membrane-bound glucosylceramidase (family GH116) remove the terminal glucose from the ceramide lipid moiety. Here, we compare enzyme differences in fold, action, dynamics, and catalytic domain stabilization by binding site occupancy. We also explore other glycosidases with reported glycosylceramidase activity, including human cytosolic β-glucosidase, intestinal lactase-phlorizin hydrolase, and lysosomal galactosylceramidase. Last, we describe the successful translation of research to practice: recombinant glycosidases and glucosylceramide metabolism modulators are approved drug products (enzyme replacement therapies). Activity-based probes now facilitate the diagnosis of enzyme deficiency and screening for compounds that interact with the catalytic pocket of glycosidases. Future research may deepen the understanding of the functional variety of these enzymes and their therapeutic potential.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ben Bdira F,Artola M,Overkleeft HS,Ubbink M,Aerts JMFGdoi
10.1194/jlr.R086629subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2262-2276issue
12eissn
0022-2275issn
1539-7262pii
jlr.R086629journal_volume
59pub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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doi:10.1194/jlr.d200013-jlr200
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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doi:10.1194/jlr.D008391
更新日期:2010-11-01 00:00:00
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1975-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
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doi:10.1194/jlr.M300339-JLR200
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journal_title:Journal of lipid research
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Previous findings with various murine tumor cell lines suggest an association between ganglioside GM3 and cell cohesive properties. The influence of GM3 on cohesion was studied in two mouse brain tumor cell lines: ependymoblastoma (EPEN) and CT-2A. In culture, the EPEN cells grow as islands and contain GM3 as the only...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
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journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Delta 6 desaturase (FADS2) is a critical bifunctional enzyme required for PUFA biosynthesis. In some organisms, FADS2s have high substrate specificity, whereas in others, they have high catalytic activity. Previously, we analyzed the molecular mechanisms underlying high FADS2 substrate specificity; in this study, we a...
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
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