Figure 1. The key hydrogen bond network in (A) the crystal structure of
BChE (PDB ID 4BDS), and in (B) the crystal structure of AChE (PDB ID
4EY4). The oxygen and nitrogen atoms are rendered with red and blue
colors, respectively. The carbon atoms in BChE and AChE are rendered
with cyan and green colors, respectively. The black dashed lines
indicate hydrogen bonds, and the red spheres at the center are the water
molecules.
In the crystal structure of AChE, as we can see from Figure 1B, such a
key hydrogen bond network also exists, and it is highly similar to that
in BChE. Therefore, just as that in BChE, the Glu202 in AChE is very
likely to be protonated in order to join and stabilize the key hydrogen
bond network. Interestingly, this hydrogen bond network has been pointed
out to be critical in stabilizing the active center, but the protonation
state of Glu202 was not mentioned.15 Thus, it is of
great interest to know what protonation state is adopted by Glu202 in
stabilizing the key hydrogen bond network, and what consequence is if
Glu202 adopts a different protonation state.
In the present work, we carried
out a series of molecular dynamics simulations to investigate the
dynamical behaviors of the key hydrogen bond network with the Glu202
adopting different protonation states. Their effects on the stability of
catalytic His447 are also examined.