DIHYDROFOLATE REDUCTASE, secondary structure 'sketch' Dihydrofolate Reductase (DHFR) is an NADPH-linked enzyme, responsible (as its name suggests) for the reduction of dihydrofolate to tetrahydrofolate. There is marked species-to-species variability in the affinity of DHFR for small-molecule inhibitors, allowing selective inhibition of the enzyme's action in an invading organism, at concentrations that will not adversely affect the DHFR of the host. A number of clinically useful drugs have been developed, and there is keen interest in structural studies on the DHFRs of various species, to provide a basis for rational development of new species-specific chemotherapeutic agents. This image shows an interactive, secondary structure representation of the DHFR from the bacterium Lactobacillus Casei. Secondary structure is a term used to describe the (usually two) energetically favourable conformations often taken up by polypeptide chains. In the alpha-helix, the regular spiral taken up by the chain is stabilised by hydrogen bonds parallel to the helix axis. In the beta-pleated sheet, extended stretches of polypeptide chain (beta strands), lying parallel with each other, are stabilised by hydrogen bonds between adjacent strands. In this image, alpha helices are shown as spirals; strands of beta- pleated sheet as arrows. The randomly folded polypeptide chain making up the rest of the structure is indicated by virtual c-alpha bonds. An image of this type, allowing real-time rotation, pan and zoom, is extremely useful in teaching fundamentals of protein structure. Additionally it is ideal for evolutionary and topographical studies of protein structures, especially when used to compare functionally or structurally related molecules.