Crystal Structure of the 6-Hydroxymethyl-7,8-Dihydropterin Pyrophosphokinase•Dihydropteroate Synthase Bifunctional Enzyme from Francisella tularensis
Figure 7
The FtHPPK module bound to Compound 1.
(A) Stereo view showing the interactions of Compound 1 (Cmpd 1) within the DHP binding pocket. The orientation is the same as that shown in Fig. 5A. Putative hydrogen-bonds are indicated as gray dashes. Two water molecules (W1 and W2) are shown as red spheres bridging between Compound 1 and loop H2. Note that the side chain of Asp101 is 50∶50 in two orientations, both of which engage Compound 1. Compound 1 is enclosed by the Fo-Fc simulated-annealing omit electron density contoured at 2.5 σ (grey mesh) and 5.0 σ (royal blue). The latter indicates the most probable location of the electron-rich nitro-moiety which dictated the fit. (B) Comparison between the binding orientations of DHP (yellow) and Compound 1. As measured with respect to their ‘nitrogen faces’, the two compounds are rotated by ∼40°. The magnesium ions in the substrate complex at the first and second positions are labeled Mg1 and Mg2, respectively, and interaction with Compound 1 causes Mg2 to bind in a new location as indicated by the arrow.