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Figure 1.
Fig. 1. Interactions of the bisubstrate inhibitor with
TmpK (a). Distance map of TP[5]A bound to TmpK[coli]. P loop
residues are marked with an asterisk. (b-d) Stereoviews. Overlay
of the TmpK[coli]-TP[5]A complex model (pink) with the
TmpK[yeast]-TP[5]A model (green) (b and c) or the
TmpK[coli]-AZTP[5]A (blue) (d). (b) Interactions of the
3'-hydroxyl of the thymidine deoxyribose. In TmpK[yeast], a
bidentate interaction between the P loop aspartic acid and the
sugar hydroxyl is observed. The binding of AZT-MP causes the P
loop to move, thus displacing the catalytic P loop arginine. In
contrast, in TmpK[coli], the interaction between Glu-12 and the
3'-hydroxyl is side-on, and the bulkier azido group does not
induce a significant movement of the P loop. (c) Similar
phosphate-arginine interactions made in TmpK[yeast] by Arg-15
and in TmpK[coli] by Arg-153. Displayed are the P loop and a
part of the Lid region. The structures were overlaid according
to the position of the bisubstrate inhibitor. (d) In the
TmpK[coli]-TP[5]A and the TmpK[coli]-AZTP[5]A complex
structures, the thymine base is at an identical position, but
the deoxyribose moiety has undergone a rigid-body rotation
caused by the azido group in the AZT-P[5]A complex. In addition,
Glu-12 has rotated slightly to provide more room for the azido
group. The rotation of the deoxyribose induces a similar
rotation of the Glu-160 side chain. As Glu-12 makes close
interactions with Asp-157, the latter carboxylic acid also
rotates slightly. b-d were generated by using BOBSCRIPT (29, 30)
and RASTER 3D (31).
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