Evolution of NAD Biosynthetic Enzymes

to expose a new hydrophobic patch that in the dimeric structure buries 890 Å2 of surface area. The hydrophobic patch is conserved throughout this family of response regulators, which suggests that it may be important for biological function. Activation would therefore require significant flexibility in the hinge or linker region and loss of interdomain contacts to allow the symmetric head-to-head dimer to form between receiver domains while accommodating the asymmetric head-to-tail structure formed by the DNA binding domains. This work extends a recent publication from the Stock laboratory on another activated OmpR/PhoB family member, ArcA, and may be generally applicable throughout this family (Toro-Roman et al., 2005). Taken together, these findings support the idea that upon phosphorylation these proteins form an active dimer along the α4-β5-α5 surface. However, important questions remain. Does the effector domain or DNA binding influence how these proteins dimerize in vivo? How does the interdomain linker region facilitate the nonsymmetrical packing of the domains in the activated structure? The answers to these and other questions will lead to a fuller understanding of the molecular mechanism of response regulator activation and will alleviate the fears of all phosphorylation phobes that this mechanism will never be unraveled. William R. McCleary Microbiology and Molecular Biology Department Brigham Young University Provo, Utah 84602