Evolution of Proenkephalin and Prodynorphin

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Abstract
SYNOPSIS. Since the discovery of the enkephalins in 1975, three separate families of opioid peptides have been identified, proopiomelanocortin, proenkephalin, and prodynorphin. The lattertwo have multiple copies of the enkephalin sequence in larger enkephalin containing polypeptides (ECPs). The amino acid and nucleotide sequences of these two proteins from human as well as other species have been determined. A comparison of each of the proteins between species indicates a number of highly conserved regions in not only the bioactive peptides but at other locations as well. A number of common features between the two proteins suggested a common ancestral protein. Using computeraided metric analysis, it is possible to align their DNA segments so thatthe cysteine residues at the amino end are aligned, as well as the enkephalin sequences at the carboxyl end. The exact alignment of the central regions is currently being studied. Metric analysis thus provides strong evidence that proenkephalin and prodynorphin diverged from a single ancestral protein.

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