Pig heart mitochondrial malate dehydrogenase (EC 1.1.1.37), which has been obtained free of electrophoretic subforms, has been shown to have a molecular weight of 67,000 and to be composed of two polypeptide chains. Comparison of these and other properties, such as amino-acid composition, isoelectric point, and keto-substrate inhibition, with those of L-3-hydroxyaeyl CoA dehydrogenase (EC 1.1.1.35), another NAD+-dependent dehydrogenase of mitochondrial origin, suggests structural similarities of the type associated with proteins possessing common evolutionary origins. This conclusion is supported by immunological crossreactivity. In view of these observations, the dissimilarity in the stereospecificity of hydrogen transfer from cofactor to substrate catalyzed by the two enzymes is attributed to 1800 rotation -in the binding orientation of the nicotinamide moiety of the NAD+, rather than to gross differences in the geometry of the active site of the two enzymes.Comparisons of the structure-function relationships of numerous proteins have provided a clearly emerging picture of the evolution of biological function within a class of proteins through selective genetic alterations leading to local changes in side chain character and environment without appreciably affecting the conformation of the polypeptide backbone. The family of serine proteases, where similarities in primary and three-dimensional structure are manifested in a variety of proteolytic enzymes with differing specificities from diverse phylogenetic origins (1)(2)(3)(4)(5), is the best documented example of this phenomenon. Altho~h less well documented at the threedimensional level, Iyaouyme and a-lactalbumin (6, 7) and nerve growth factor and insulin (8)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.