Investigating Phosphorylation-Induced Conformational Changes in WNK1 Kinase by Molecular Dynamics Simulations.

ABSTRACT: The With-No-Lysine (WNK) kinase is considered to be a master regulator for various cation-chloride cotransporters involved in maintaining cell-volume and ion homeostasis. Here, we have investigated the phosphorylation-induced structural dynamics of the WNK1 kinase bound to an inhibitor via atomistic molecular dynamics simulations. Results from our simulations show that the phosphorylation at Ser³⁸² could stabilize the otherwise flexible activation loop (A-loop). The intrahelix salt-bridge formed between Arg²⁶⁴ and Glu²⁶⁸ in the unphosphorylated system is disengaged after the phosphorylation, and Glu²⁶⁸ reorients itself and forms a stable salt-bridge with Arg³⁴⁸. The dynamic cross-correlation analysis shows that phosphorylation diminish

SUBMITTER: Jonniya NA 

PROVIDER: S-EPMC6812135 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature