Phosphate transfer in hexokinase

Question

In glycolysis, hexokinase transfers a phosphate group from ATP to glucose. This is an example of the coupling of an exergonic reaction with an endergonic reaction, such that the endergonic reaction is forced to occur.

Please explain how the enzyme ensures that the phosphate group ends up on the glucose and does not simply get transferred to a water molecule.

In trying to work out this problem, I came up with the following explanation:

1. The hexokinase has two different states: open and closed form.
2. In the open state, only glucose can bound thus the enzyme will change its shape
3. When the enzyme change its shape, the enzyme will close.
4. Once the enzyme is in the close state, the enzyme can bind the ATP (the phosphate to the glucose).

This sequence will make the phosphorylation possible without getting the phosphate transferred to a water molecule.

So, is the explanation correct or am I wrong?

Answer 1

In crystals, hexokinase is able to bind to ATP (or ADP or AMP-PNP) in the absence off glucose. It has a miniscule ATPase activity (40,000 times slower than the hexokinase activity.

Source: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/j.1432-1033.1970.tb01075.x

The two pieces of evidence combined show that ATP does not "have to wait" for glucose to bind and the enzyme to close. Comparing the Km of the hexokinase to the ATPase activity, it does seem the ATP binds a bit tighter when glucose is bound.

[quoted by OP] This is an example of the coupling of an exergonic reaction with an endergonic reaction, such that the endergonic reaction is forced to occur.

This is not the best example of coupling because the reaction is a phosphate transfer from ATP to glucose, an exergonic reaction. All the enzyme has to do is to catalyze that reaction without letting water in the position that the glucose hydroxyl group occupies when bound. Better examples are e.g. ion pumps where ATP does get hydrolized to form ADP and phosphate. Here, the enzyme has to be a little more "sophisticated" to couple the two reactions.