title: Dogfish insulin. Primary structure, conformation and biological properties of an elasmobranchial insulin.
abstract: Insulin from an elasmobranch, the spiny dogfish (Squalus acanthias) has been purified to near homogeneity by means of acid-ethanol extraction and salt precipitation. The amino acid sequences of the performic-acid-oxidised A and B chains have been determined and exhibit some unusual features. The A chain contains a total of 22 amino acids; only the insulin from coypu (a member of the Rodentia suborder, Hystricomorpha), has previously been reported to contain an extension past the A21 asparagine. The B10 histidine, which is involved in the formation of the insulin hexamers in higher vertebrates through the co-ordination of zinc, is present in this elasmobranch insulin. Several substitutions relative to bovine insulin occur in the proposed receptor binding region (A5Gln leads to His, B21Glu leads to Pro, B22Arg leads to Lys, B25Phe leads to Tyr). In spite of these substitutions, the maximal response in the rat epididymal fat cell assay is the same for bovine and dogfish insulins; the concentration required to produce the half-maximal response is, however, approximately threefold greater for dogfish insulin than that of bovine insulin. The use of interactive computer graphics model-building predicts that the dogfish insulin can attain a three-dimensional structure very similar to that of bovine insulin; circular dichroic spectra are presented which support the model-building studies.
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002942:Circular Dichroism; D003201:Computers; D004284:Dogfish / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000302:isolation & purification* / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D012754:Sharks / Q000378:metabolism*; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D007328:Insulin