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Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-147 Sentence denotes Cantu syndrome-associated SUR2 (ABCC9) mutations in distinct structural domains result in KATP channel gain-of-function by differential mechanisms.
T2 148-359 Sentence denotes The complex disorder Cantu syndrome (CS) arises from gain-of-function mutations in either KCNJ8 or ABCC9, the genes encoding the Kir6.1 and SUR2 subunits of ATP-sensitive potassium (KATP) channels, respectively.
T3 360-467 Sentence denotes Recent reports indicate that such mutations can increase channel activity by multiple molecular mechanisms.
T4 468-699 Sentence denotes In this study, we determined the mechanism by which KATP function is altered by several substitutions in distinct structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E, M1060I, and R1154Q/R1154W in TMD2.
T5 700-944 Sentence denotes We engineered substitutions at their equivalent positions in rat SUR2A (D207E, Y981S, G985E, M1056I, and R1150Q/R1150W) and investigated functional consequences using macroscopic rubidium (86Rb+) efflux assays and patch-clamp electrophysiology.
T6 945-1180 Sentence denotes Our results indicate that D207E increases KATP channel activity by increasing intrinsic stability of the open state, whereas the cluster of Y981S/G985E/M1056I substitutions, as well as R1150Q/R1150W, augmented Mg-nucleotide activation.
T7 1181-1325 Sentence denotes We also tested the responses of these channel variants to inhibition by the sulfonylurea drug glibenclamide, a potential pharmacotherapy for CS.
T8 1326-1437 Sentence denotes None of the D207E, Y981S, G985E, or M1056I substitutions had a significant effect on glibenclamide sensitivity.
T9 1438-1530 Sentence denotes However, Gln and Trp substitution at Arg-1150 significantly decreased glibenclamide potency.
T10 1531-1668 Sentence denotes In summary, these results provide additional confirmation that mutations in CS-associated SUR2 mutations result in KATP gain-of-function.
T11 1669-1902 Sentence denotes They help link CS genotypes to phenotypes and shed light on the underlying molecular mechanisms, including consequences for inhibitory drug sensitivity, insights that may inform the development of therapeutic approaches to manage CS.