| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-136 |
Sentence |
denotes |
Nicotiana benthamiana α-galactosidase A1.1 can functionally complement human α-galactosidase A deficiency associated with Fabry disease. |
| T2 |
137-434 |
Sentence |
denotes |
α-Galactosidases (EC 3.2.1.22) are retaining glycosidases that cleave terminal α-linked galactose residues from glycoconjugate substrates. α-Galactosidases take part in the turnover of cell wall-associated galactomannans in plants and in the lysosomal degradation of glycosphingolipids in animals. |
| T3 |
435-661 |
Sentence |
denotes |
Deficiency of human α-galactosidase A (α-Gal A) causes Fabry disease (FD), a heritable, X-linked lysosomal storage disorder, characterized by accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). |
| T4 |
662-729 |
Sentence |
denotes |
Current management of FD involves enzyme-replacement therapy (ERT). |
| T5 |
730-894 |
Sentence |
denotes |
An activity-based probe (ABP) covalently labeling the catalytic nucleophile of α-Gal A has been previously designed to study α-galactosidases for use in FD therapy. |
| T6 |
895-1127 |
Sentence |
denotes |
Here, we report that this ABP labels proteins in Nicotiana benthamiana leaf extracts, enabling the identification and biochemical characterization of an N. benthamiana α-galactosidase we name here A1.1 (gene accession ID GJZM-1660). |
| T7 |
1128-1322 |
Sentence |
denotes |
The transiently overexpressed and purified enzyme was a monomer lacking N-glycans and was active toward 4-methylumbelliferyl-α-d-galactopyranoside substrate (Km = 0.17 mm) over a broad pH range. |
| T8 |
1323-1518 |
Sentence |
denotes |
A1.1 structural analysis by X-ray crystallography revealed marked similarities with human α-Gal A, even including A1.1's ability to hydrolyze Gb3 and lyso-Gb3, which are not endogenous in plants. |
| T9 |
1519-1691 |
Sentence |
denotes |
Of note, A1.1 uptake into FD fibroblasts reduced the elevated lyso-Gb3 levels in these cells, consistent with A1.1 delivery to lysosomes as revealed by confocal microscopy. |
| T10 |
1692-1952 |
Sentence |
denotes |
The ease of production and the features of A1.1, such as stability over a broad pH range, combined with its capacity to degrade glycosphingolipid substrates, warrant further examination of its value as a potential therapeutic agent for ERT-based FD management. |
