Large-scale conformational changes and redistribution of surface negative charge upon sugar binding dictate the fidelity of phosphorylation in Vibrio cholerae fructokinase.

ABSTRACT: Fructokinase (FRK) catalyzes the first step of fructose metabolism i.e., D-fructose to D-fructose-6-phosphate (F6P), however, the mechanistic insights of this reaction are elusive yet. Here we demonstrate that the putative Vibrio cholerae fructokinase (VcFRK) exhibit strong fructose-6-kinase activity allosterically modulated by K⁺/Cs⁺. We have determined the crystal structures of apo-VcFRK and its complex with fructose, fructose-ADP-Ca²⁺, fructose-ADP-Ca²⁺-BeF₃^-. Collectively, we propose the catalytic mechanism and allosteric activation of VcFRK in atomistic details explaining why K⁺/Cs⁺ are better activator than Na⁺. Structural results suggest that apo VcFRK allows entry of fructose in the a

SUBMITTER: Paul R 

PROVIDER: S-EPMC6240065 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature