Conformational transition pathway of R308K mutant glucokinase in the presence of the glucokinase activator YNKGKA4.

ABSTRACT: Glucokinase (GK) plays a vital role in the control of blood glucose levels and its altered activity can lead to the development of forms of diabetes. We have previously identified a mutant GK (R308K) in patients with type 2 diabetes with reduced enzyme activity. In the present study, the activation mechanism of GK from super-open to the closed state under wild-type and mutant conditions in the presence of the novel aminophosphonate derivative YNKGKA4 (an allosteric activator of GK) was characterized via a series of molecular dynamics simulations. A reliable conformational transition pathway of GK was observed from super-open to closed state during trajectory analysis. Glucose was also observed to modulate its binding orientation in the active site but with stable moments in the cavity. The

SUBMITTER: Yellapu NK 

PROVIDER: S-EPMC6070654 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature