Activity Regulation and Conformation Response of Janus Kinase 3 Mediated by Phosphorylation: Exploration from Correlation Network Analysis and Markov Model DOI

Jian‐Zhong Chen,

Jian Wang, Wanchun Yang

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

The activity of the enzyme JAK3 is modulated by tyrosine phosphorylation, yet underlying molecular details remain not fully understood. In this study, we employed a GaMD trajectory-based Markov model and correlation network analysis (CNA) to investigate impact single phosphorylation (SP) at Y980 (pY980) double (DP) Y980/Y981 (pY980/pY981) on conformational dynamics bound inhibitors IZA MI1. indicated that both SP DP result in fewer states significantly influence P-loop, αC-helix, loop1-loop3, while maintaining hinge region's high rigidity. CNA findings revealed alters communication among different structural regions JAK3, providing rational explanation for how affects distant P-loop loop1-loop3. Moreover, changes mediated further affect interactions between hot spots (L828, V836, E903, Y904, L905, L956) JAK3. This work offers valuable theoretical insights into mechanisms regulate activity.

Язык: Английский

Activity Regulation and Conformation Response of Janus Kinase 3 Mediated by Phosphorylation: Exploration from Correlation Network Analysis and Markov Model DOI

Jian‐Zhong Chen,

Jian Wang, Wanchun Yang

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

The activity of the enzyme JAK3 is modulated by tyrosine phosphorylation, yet underlying molecular details remain not fully understood. In this study, we employed a GaMD trajectory-based Markov model and correlation network analysis (CNA) to investigate impact single phosphorylation (SP) at Y980 (pY980) double (DP) Y980/Y981 (pY980/pY981) on conformational dynamics bound inhibitors IZA MI1. indicated that both SP DP result in fewer states significantly influence P-loop, αC-helix, loop1-loop3, while maintaining hinge region's high rigidity. CNA findings revealed alters communication among different structural regions JAK3, providing rational explanation for how affects distant P-loop loop1-loop3. Moreover, changes mediated further affect interactions between hot spots (L828, V836, E903, Y904, L905, L956) JAK3. This work offers valuable theoretical insights into mechanisms regulate activity.

Язык: Английский

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