Structural basis for the subtype-selectivity of KCa2.2 channel activators DOI
Miao Zhang, Young-Woo Nam,

Alena Ramanishka

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 16, 2025

Small-conductance (K Ca 2.2) and intermediate-conductance 3.1) 2+ -activated K + channels are gated by a -calmodulin dependent mechanism. NS309 potentiates the activity of both 2.2 3.1, while rimtuzalcap selectively activates 2.2. Rimtuzalcap has been used in clinical trials for treatment spinocerebellar ataxia essential tremor. We report cryo-electron microscopy structures bound with rimtuzalcap, addition to 3.1 NS309. The different conformations calmodulin cytoplasmic HC helices two underlie subtype-selectivity Calmodulin's N-lobes structure far apart undergo conformational changes accommodate either or rimtuzalcap. closer each other constrained which allows binding but not bulkier These provide framework structure-based drug design targeting channels.

Язык: Английский

Structural basis for the subtype-selectivity of KCa2.2 channel activators DOI
Miao Zhang, Young-Woo Nam,

Alena Ramanishka

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 16, 2025

Small-conductance (K Ca 2.2) and intermediate-conductance 3.1) 2+ -activated K + channels are gated by a -calmodulin dependent mechanism. NS309 potentiates the activity of both 2.2 3.1, while rimtuzalcap selectively activates 2.2. Rimtuzalcap has been used in clinical trials for treatment spinocerebellar ataxia essential tremor. We report cryo-electron microscopy structures bound with rimtuzalcap, addition to 3.1 NS309. The different conformations calmodulin cytoplasmic HC helices two underlie subtype-selectivity Calmodulin's N-lobes structure far apart undergo conformational changes accommodate either or rimtuzalcap. closer each other constrained which allows binding but not bulkier These provide framework structure-based drug design targeting channels.

Язык: Английский

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