Two-dimensional crystal structure of aquaporin-4 bound to the inhibitor acetazolamide.

ABSTRACT: Acetazolamide (AZA) reduces the water permeability of aquaporin-4, the predominant water channel in the brain. We determined the structure of aquaporin-4 in the presence of AZA using electron crystallography. Most of the features of the 5-Å density map were consistent with those of the previously determined atomic model. The map showed a protruding density from near the extracellular pore entrance, which most likely represents the bound AZA. Molecular docking simulations supported the location of the protrusion as the likely AZA-binding site. These findings suggest that AZA reduces water conduction by obstructing the pathway at the extracellular entrance without inducing a large conformational change in the protein.

SUBMITTER: Kamegawa A 

PROVIDER: S-EPMC4817316 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature