From analysis to synthesis: new ligand binding sites on the lactate dehydrogenase framework. Part II.

In Part I of this article (published in the March issue of TIBS1), substrate-binding and catalysis in lactate dehydrogenase were examined by genetic modification of the protein structure and analysis of the functional consequences. In Part II, the conclusions are used in the design and synthesis of two modified forms of the enzyme; one in which the substrate specificity is shifted to produce a more effective malate dehydrogenase than that isolated from the host organism and one which no longer requires its allosteric activator (fructose 1,6-bisphosphate).