The NT5E variants in the crystal structure of the enzyme. (A) NT5E A62 (magenta) directly interacts with I320 and K321 (yellow) in the α-helix that connects the 2 protein domains and works as a hinge for the conformational change between the open and closed states. The A62S variant is predicted to impede the conformational change of the enzyme from the open state to the closed state. (B) V278 (magenta), interacting with L290 and V240 (yellow), is buried within the core of the N-terminal domain. The V278I variant is predicted to affect the folding of this domain and the conformation of the catalytic pocket. (C) The side chain of R354 (magenta) forms a hydrogen bond with adenosine. The R354C variant is predicted to disrupt the binding of adenosine.27 (D) R401 (magenta) interacts with R480 (yellow) from the other chain in the closed state. The R401C variant is predicted to impede the NT5E dimerization and the conformational change of the enzyme from the open state to the closed state. All structures shown are in the closed state. The substrate adenosine is displayed in the sphere model, and the highlighted amino acids are displayed in the stick model.
