Complementary DNA sequences of renin. State-of-the-art review.

Abstract

The primary structure of human renin precursor was deduced from its complementary DNA (cDNA) sequence. The predicted sequence consists of 406 amino acids with a pre- and a prosegment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology, especially in the catalytically important region, was found upon comparison of the mouse and human renins. An overall homology, including presequence between the two renins, is 68.7%. Close similarities were also observed in the primary structure of renins and other aspartyl proteinases with defined three-dimensional structures, suggesting a tertiary structure for renin that is similar to the other enzymes. A bilobal model of the tertiary structure of human renin with two approximately equal domains separated by a cleft was constructed using the homology of amino acid sequence of renins and other aspartyl proteinases. These results indicate that human kidney renin is homologous with mouse submandibular renin in primary and tertiary structures, proteolytic processing, and catalytic apparatus with small differences. The major structural difference distinguishing the two renins was the presence of the two possible glycosylation sites in human kidney renin, which was not observed in mouse submandibular gland renin.