Crystal Structure of the 6-Hydroxymethyl-7,8-Dihydropterin Pyrophosphokinase•Dihydropteroate Synthase Bifunctional Enzyme from Francisella tularensis
Figure 2
The primary structure of the HPPK-DHPS bifunctional enzyme from Francisella tularensis and its homology to other HPPK and DHPS enzymes.
The organisms shown are Francisella tularensis (Ft), Saccharomyces cerevisiae (Sc), Yersinia pestis (Yp), Escherichia coli (Ec) and Bacillus anthracis (Ba), and numbering is with respect to the Ft enzyme. Secondary structure elements and key structural regions are labeled according to Fig. 3A. Strictly conserved regions are blocked in red, and conserved regions are boxed. Important loop regions are highlighted and labeled according to their domain association. (A) Multiple sequence alignment of the HPPK module. Residues that contribute to substrate binding are shown as blue triangles. The conserved motif that binds Mg2+ is shown as gray circles within blue triangles. (B) Alignment of the DHPS module. The inter-domain linker regions of F. tularensis and S. cerevisiae are highlighted in green and the corresponding β-hairpin of monofunctional DHPS is highlighted in orange. Residues that interact with substrates are indicated as purple triangles. Residues known to contribute to sulfonamide drug resistance are indicated by red circles. The missing Dα8 helix at the C-terminus is highlighted in purple. Sequence alignments were performed using ClustalW [39] and analyzed using ESPript2.2 [54].