Mammalian Hexokinase I

Figure 1. Structure description of Hexokinase I. The C-terminal domain (Catalytic domain) is initially displayed in a cartoon diagram with coloring for the secondary structure, shows the open twisted beta-sheet motif with two strands being anti-parallel to the rest.Then will show the position of the binding site (Glc/ADP) in the cleft between the large (blue) and the small (yellow) lobe, and finally will show the Catalytic and Regulatory domains highlighting the interaction regions (loops) between them (green)

Figure 2. Inhibition mechanism by Glc-6-P. An initial zoom into the Regulatory (N-terminal) domain shows the interaction of the inhibitor (Glc-6-P) with the Ser449 of the transitional α-helix (green). This interaction stabilized the relative position between the Regulatory and Catalytic domain, with further stabilizes a specific conformation of flexible subdomain in the Catalytic domain (green). Then, in the Catalytic (C-terminal) domain the ATP and Glucose (Glc) binding site are shown in a spacefill diagram (orange, large lobe and yellow, small lobe). The stabilized conformation of flexible subdomain by the binding of Glc-6-P in the Regulatory domain, projects Thr784 into the binding pocket of ATP and inhibiting its binding.

Figure 3. Release of Glc-6-P inhibition by Pi. First it shown Allosteric binding site (Regulatory domain), in this case Pi is binding in stead of Glc-6-P (Pi binds in the position of the phosphoryl group of Glc-6-P). As there is no interaction with Ser449 a torsion of the transitional α-helix (green) changes the relative position of the Regulatory domain with respect to the Catalytic domain. As a consequence a new conformation of the flexible subdomain (green) is obtain in the Catalytic domain changing the position of Thr784 that now allows the binding of ATP.