Primary structure of insulin from the african lungfish, Protopterus annectens

Among the extant Sarcopterygii, the interrelationship between the Dipnoi (lungfishes), Actinistia (coelacanths), and Tetrapoda (tetrapods) is controversial. Insulin has been purified from an extract of the pancreas of the African lungfish Protopterus annectens and its primary structure established as A-chain, Gly-Ile-Val-Glu-Gln-Cys-Cys-His-Lys-Pro10-Cys-Ser-Leu- Tyr -Glu-Leu-Glu-Asn-Tyr-Cys20-Asn-Val-Pro; and B-chain, Ala-Val-Leu-Asn-Gln-His-Leu-Cys-Gly-Ser10-His-Leu-Val- Glu- Ala-Leu-Tyr-Leu-Val-Cys20-Ala-Asp-Asn-Gly-Phe- Phe-Tyr-Lys-Pro-Ser30-Gly. Lungfish insulin contains unusual structural features, such as the dipeptide extension to the C-terminus of the A-chain and the substitution Arg --> Asn at position B-23 in the putative receptor binding region of insulin, which may be expected to influence appreciably its biological potency relative to mammalian insulins. Lungfish insulin also contains amino acid substitutions such as Gly --> Ala at position B-21, Glu --> Asp at position B-22, and a Lys --> Ser residue at position B-30, previously found in insulins from amphibia. This observation is consistent with paleontological data suggesting that lungfish and amphibia share a close phylogenetic relationship.