Enzymes are complex macromolecules capable of catalyzing a wide variety of chemical
reactions with high efficiency. Nonetheless, biological catalysis can be rudimentary. Here …

Biological systems can gain complexity over time. While some of these transitions are likely
driven by natural selection, the extent to which they occur without providing an adaptive …

We present a potential mechanism for emergence of catalytic activity that is essential for
survival, from a non-catalytic protein fold. The type B dihydrofolate reductase (DfrB) family of …

Type B dihydrofolate reductase (dfrb) genes were identified following the introduction of
trimethoprim in the 1960s. Although they intrinsically confer resistance to trimethoprim (TMP) …

Trimethoprim (TMP) is widely used to treat infections in humans and in livestock,
accelerating the incidence of TMP resistance. The emergent and largely untracked type II …

Protein engineering, the process by which novel proteins with desired properties are
developed, has grown by leaps and bounds since the first examples of protein mutagenesis …

Biological systems can gain complexity over time. While some of these transitions are likely
driven by natural selection, the extent to which they occur without providing an adaptive …

R67 dihydrofolate reductase (DHFR) is a homotetramer with a single active site pore and no
sequence or structural homology with chromosomal DHFRs. The R67 enzyme provides …

Drug design by methods such as fragment screening requires effective solubilization of
millimolar concentrations of small organic compounds while maintaining the properties of …

Dihydrofolate reductase (DHFR), a key enzyme in tetrahydrofolate-mediated biosynthetic
pathways, has a structural motif known to be highly conserved over a wide range of …