Crystal Structure of the 6-Hydroxymethyl-7,8-Dihydropterin Pyrophosphokinase•Dihydropteroate Synthase Bifunctional Enzyme from Francisella tularensis
Figure 5
The FtHPPK and FtDHPS modules bound to substrates.
(A) Stereo view of the FtHPPK module showing the detailed interactions with AMPcPP and DHP. Both substrates are covered with transparent molecular surfaces and gray dashed lines indicate putative hydrogen-bond interactions. Residues that contribute to substrate binding are labeled and shown in blue sticks. The inter-domain linker is colored green and a dashed line indicates the position of the carboxy-terminal FtDHPS module. (B) Electron densities for the nucleotide analog AMPcPP (purple) and DHP (yellow) bound to the HPPK module. Two Mg2+ ions (gray spheres labeled Mg1 and Mg2), and an active site water (red sphere labeled W1) are also shown. The arrow indicates how the 6-hydroxymethyl group of DHP is appropriately oriented towards the pyrophosphate moiety of AMPcPP for in-line phosphoryl transfer. (C) Stereo view of the interactions between DHP and the FtDHPS module. DHP is bound within the TIM-barrel (light pink, β-barrel), and the residues that mediate the interaction are labeled and shown in pink sticks. Three structural water molecules are shown as red spheres and are labeled W2, W3 and W4. The location of the FtHPPK module is indicated by a dashed line that extends from the inter-domain linker (green). (D) Electron density for the molecule of DHP (yellow) which bound in the pterin pocket of the FtDHPS module. In (B) and (D), the Fo-Fc simulated-annealing omit electron densities are contoured at 3.5 σ.