PRIMARY STRUCTURE OF INSULIN FROM THE AFRICAN LUNGFISH, PROTOPTERUS ANNECTENS

Among the extant Sarcopterygii, the interrelationship between the Dipn oi (lungfishes), Actinistia (coelacanths), and Tetrapoda (tetrapods) i s controversial. Insulin has been purified from an extract of the panc reas of the African lungfish Protopterus annectens and its primary str ucture established as A-chain, r-Leu-Tyr-Glu-Leu-Glu-Asn-Tyr-Cys(20)-A sn-Val-Pro; and B-chain, 0)-His-Leu-Glu-Ala-Leu-Tyr-Leu-Val-Cys(20)-Al a-Asp -Asn-Gly-Phe-Phe-Tyr-Lys-Pro-Ser(30)-Gly. Lungfish insulin conta ins unusual structural features, such as the dipeptide extension to th e C-terminus of the A-chain and the substitution Arg --> Asn at positi on B-23 in the putative receptor binding region of insulin, which may be expected to influence appreciably its biological potency relative t o mammalian insulins. Lungfish insulin also contains amino acid substi tutions 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 paleontolo gical data suggesting that lungfish and amphibia share a close phyloge netic relationship. (C) 1997 Academic Press.