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Figure 4.
Figure 4. The F105Y mutant adopts a partially closed
conformation even in the presence of ADP. (a) Stereoview of the
overlay between the complex of TMP and ADP with wild-type TMPK
and the F105Y mutant, respectively. In the wild-type complex
structure (depicted in pink), seven interconnected water
molecules are observed to stabilize the open conformation. The
presence of the hydroxyl group of Y105 hinders the formation of
such a water structure, thereby destabilizing the open
conformation. In addition, the hydroxyl moiety interacts with
the side-chain of Gln157, which interacts with the amide
nitrogen atom of the P-loop Asp15 (broken lines), resulting in
the stabilization of the closed conformation. (b) To illustrate
the steric clash that would ensue due to the introduced tyrosine
hydroxyl moiety (instead of Phe), the structure observed in the
open TMP-ADP complex is depicted with its interconnecting water
structure, and the tyrosine residue (pink) from the F105Y
structure.
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