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Figure 3.
Figure 3. The 60-fold reduced catalytic rate with AZTMP in
comparison to TMP suggests that TMPK can nevertheless adopt the
partially closed (i.e. active) conformation despite the presence
of the azido group. Overlay of the bisubstrate inhibitor
complexes with either TP[5]A, shown in pink and modeled as TMP
and ATP, and AZTP[5]A (modeled as AZTMP and ATP) reveal that the
side-chain of Asp15 points away from the 3' substituent in the
case of AZTP[5]A, but makes an interaction with the 3'-hydroxyl
group in the case of TP[5]A. Only the fully closed conformation
was observed for the P-loop in the presence of TP[5]A, while
both the open and closed P-loop conformations were observed in
the presence of AZTP[5]A, again suggesting a higher barrier for
reaching the closed conformation in the presence of the azido
group.
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