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Biochemical characterization and identification of the catalytic residues of a family 43 beta-D-xylosidase from Geobacillus stearothermophilus T-6.
TLDR
Kinetic analysis and characterization of a family 43 beta-xylosidase from Geobacillus stearothermophilus T-6 provide the first unequivocal evidence regarding the exact roles of the catalytic residues in an inverting GH43 glycosidase. Expand
Crystal structure and snapshots along the reaction pathway of a family 51 α‐L‐arabinofuranosidase
TLDR
High‐resolution crystal structures of α‐L‐arabinofuranosidase from Geobacillus stearothermophilus T‐6, a family 51 glycosidase, are described and represent two stable states in the double displacement mechanism, and allow thorough examination of the catalytic mechanism. Expand
Designer Aminoglycosides That Selectively Inhibit Cytoplasmic Rather than Mitochondrial Ribosomes Show Decreased Ototoxicity
TLDR
Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosome show decreased ototoxicity, highlighting the benefit of a mechanism-based drug redesign strategy that can maximize the translational value of “readthrough therapy” while mitigating drug-induced side effects. Expand
Identification of the Catalytic Residues in Family 52 Glycoside Hydrolase, a β-Xylosidase from Geobacillus stearothermophilus T-6*
TLDR
Two catalytic mutants of a β-xylosidase from Geobacillus stearothermophilus T-6 were subjected to detailed kinetic analysis to verify their role in catalysis, and the pH dependence profile of the mutant enzyme revealed that acid catalysis is absent. Expand
Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model
TLDR
Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2R168X mouse model and NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients. Expand
Attenuation of Nonsense-Mediated mRNA Decay Enhances In Vivo Nonsense Suppression
TLDR
It is demonstrated that NMD attenuation significantly enhances suppression therapy in vivo, and co-administration of NMDI-1 with the PTC suppression drug gentamicin enhanced alpha-L-iduronidase activity compared to gentamic in, leading to a greater reduction of GAG storage in mouse tissues, including the brain. Expand
Repairing faulty genes by aminoglycosides: development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations.
New pseudo-di- and pseudo-trisaccharide derivatives of the aminoglycoside drug G418 were designed, synthesized and their ability to readthrough nonsense mutations was examined in both in vitro and exExpand
The identification of the acid–base catalyst of α‐arabinofuranosidase from Geobacillus stearothermophilus T‐6, a family 51 glycoside hydrolase
TLDR
Data from kinetic experiments, pH profiles, azide rescue, and the identification of the xylopyranosyl azide product provide firm support to the assignment of Glu175 as the acid–base catalyst of AbfA T‐6. Expand
The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua-W392X mouse.
TLDR
Overall, NB84 suppressed the Idua-W392X nonsense mutation much more efficiently than any of the other compounds tested, suggesting that NB84-mediated suppression therapy has the potential to attenuate the MPS I-H disease phenotype. Expand
Glutamic acid 160 is the acid‐base catalyst of β‐xylosidase from Bacillus stearothermophilus T‐6: a family 39 glycoside hydrolase
TLDR
A β‐xylosidase from Bacillus stearothermophilus T‐6 was cloned, overexpressed in Escherichia coli and purified to homogeneity to support the assignment of Glu160 as the acid‐base catalytic residue. Expand
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