Purification and characterization of islet hormones (insulin, glucagon, pancreatic, polypeptide and somatostatin) from the Burmese python, Python molurus.
Insulin was purified from an extract of the pancreas of the Burmese python, Python molurus (Squamata:Serpentes) and its primary structure established as: A Chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Glu-Asn-Thr10-Cys-Ser-Leu-Tyr-Glu-Leu- Glu-Asn-Tyr-Cys20-Asn. B-Chain: Ala-Pro-Asn-Gln-His-Leu-Cys-Gly-Ser-His10-Leu-Val-Glu-Ala-Leu-Tyr- Leu-Val-Cys-Gly20-Asp-Arg-Gly-Phe-Tyr-Tyr-Ser-Pro-Arg-Ser30. With the exception of the conservative substitution Phe --> Tyr at position B25, those residues in human insulin that comprise the receptor-binding and those residues involved in dimer and hexamer formation are fully conserved in python insulin. Python insulin was slightly more potent (1.8-fold) than human insulin in inhibiting the binding of [125I-Tyr-A14] insulin to the soluble full-length recombinant human insulin receptor but was slightly less potent (1.5-fold) than human insulin for inhibiting binding to the secreted extracellular domain of the receptor. The primary structure of python glucagon contains only one amino acid substitution (Ser28 --> Asn) compared with turtle/duck glucagon and python somatostatin is identical to that of mammalian somatostatin-14. In contrast, python pancreatic polypeptide (Arg-Ile-Ala-Pro-Val-Phe-Pro-Gly-Lys-Asp10-Glu-Leu-Ala-Lys-Phe- Tyr20-Thr-Glu-Leu-Gln-Gln-Tyr-Leu-Asn-Ser-Ile30-Asn-Arg-Pro-Arg -Phe.NH2) contains only 35 instead of the customary 36 residues and the amino acid sequence of this peptide has been poorly conserved between reptiles and birds (18 substitutions compared with alligator and 20 substitutions compared with chicken).
Conlon
J M
JM
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA. jmconlon@creighton.edu
Secor
S M
SM
Adrian
T E
TE
Mynarcik
D C
DC
Whittaker
J
J
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D017821:Boidae; D005260:Female; D005934:Glucagon / Q000737:chemistry / Q000302:isolation & purification*; D006801:Humans; D007328:Insulin / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D010191:Pancreatic Polypeptide / Q000737:chemistry / Q000302:isolation & purification*; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013004:Somatostatin / Q000737:chemistry / Q000302:isolation & purification*
D000596:Amino Acids; D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D011972:Receptor, Insulin