Rational design of an inhibitor of dethiobiotin synthetase; interaction of 6-hydroxypyrimindin-4(3H)-one with the adenine base binding site

Modelling of the H-bonding interactions involved in the binding of the adenine base component of ATP to E. coli dethiobiotin synthetase (DTBS) suggested that 6-hydroxypyrimidin-4(3H)-one (6-HP4) should selectively bind to this site in the enzyme. Kinetic studies show that 6-HP4 is a competitive inhibitor of DTBS and x-ray crystallography shows that 6-HP4 binds specifically in the purine base binding site of the enzyme.     

Antibiotics as inhibitors of nucleic acid and protein synthesis

The antibiotics of the rifamycin, actinomycin, chromomycin, and anthracycline groups have been found to be specific inhibitors for the DNA-controlled synthesis of RNA in vitro. Streptomycin, chloramphenicol, and puromycin can specifically suppress certain steps in the biosynthesis of proteins. The investigation of the mode of action of such substances may help us to gain a better insight into the transmission of hereditary information.