Water-mediated proton switches

Figure 2-4. A simplified scheme of the proposed water-gated mechanism of proton translocation. Each numbered state shows haem a and the binuclear site (left and right rectangles, respectively) the A-propionate of haem is shown schematically. Three water molecules (oxygen in red hydrogen in yellow) are shown to mediate Grotthuss proton transfer from the glutamic acid (GLU-OH) to the propionate or the binuclear site, respectively. In state 1, an electron is transferred to haem a. The formed electric field between the redox sites orientates the water molecules towards the propionate (state 2). In state 3, electron transfer to the binuclear site is accompanied by proton transfer via the propionate a proton is deposited above haem and the glutamate is reprotonated via the D-pathway (state 4). The switch of electric field orientation reorientates the water array towards the binuclear site (state 5). Finally, a proton is transferred to this site, and the first proton is ejected (state 6). Reprotonation of the glutamate transfers the system back to state 1. For details, see the text and ref. 17.

Fructose 1,6-diphosphatase hydrolyses off the 1-phosphate in the step which commits the substrate to gluconeogenesis. The mammalian enzyme, a homodimer, is richly allosteric, as befits an enzyme at a metabolic branchpoint. It catalyses a single displacement, mediated by no less than four metal ions three Mg " sites and one K " site have been observed in the crystal structure. The nucleophilic water may be activated by proton transfer from Glu98. The very large claim has been made that by alteration of the conditions of crystallisation, the on-enzyme equilibrium can be switched from fructose-6-phosphate and inorganic phosphate to fructose-6-phosphate and metaphosphate. Given the... 

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