title: Four new monomeric insulins obtained by alanine scanning the dimer-forming surface of the insulin molecule.
abstract: The residues A21Asn, B12Val, B16Tyr, B24Phe, B25Phe, B26Tyr and B27Thr, buried in the dimer of insulin, were identified by means of alanine-scanning mutagenesis. The receptor binding activity, in vivo biological potency and self-association properties of the seven single alanine human insulin mutants were determined. Four of the seven single alanine mutants, [B12Ala]human insulin, [B16Ala]human insulin, [B24Ala]human insulin and [B26Ala]human insulin, are monomeric insulin, which indicates that B12Val, B16Tyr, B24Phe and B26Tyr are crucial for the formation of insulin dimer. The monomeric [B16Ala]human insulin and [B26Ala]human insulin retain 27 and 54% receptor binding activity, respectively, and nearly the same in vivo biological potency compared with native insulin, so they could be developed as the fast-acting insulin.
authors.affiliation: State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Shi
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Guo
authors.forename: Y H
authors.initials: YH
authors.lastname: Tang
authors.forename: Z S
authors.initials: ZS
authors.lastname: Qiao
authors.forename: Z H
authors.initials: ZH
authors.lastname: Liang
authors.forename: Y M
authors.initials: YM
authors.lastname: Feng
mesh_terms: D000409:Alanine / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D003001:Cloning, Molecular; D019281:Dimerization; D004926:Escherichia coli; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D007328:Insulin; D011972:Receptor, Insulin; D000409:Alanine