Structural contribution of the A-chain loop in relaxin.
Site-directed sequential disulfide bond formation has been used to synthesize relaxin analogs with modifications in the A chain loop (A10-A15). In the four different derivatives either the amino acid residues between the cysteines (A12-A14) were replaced or the intrachain disulfide bond (A10-A15) was eliminated. The substitution of the human relaxin II sequence (His-Val-Gly; A12-14) by the corresponding insulin sequence (Thr-Ser-Ile) or the hydrocarbon chain of omega-aminooctanoic acid (Aoc) caused significant loss of biological activity. Similar observations were made when the pair of cysteines (A10-A15) was replaced by either alanine or serine, whereby serine disturbs more than alanine. It is suggested that the structural features of the A chain loop not only make important contributions to the active conformation of relaxin but also that the structural requirements of insulin and relaxin are different.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, USA.
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D000595:Amino Acid Sequence; D002210:Caprylates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000737:chemistry; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011487:Protein Conformation; D012065:Relaxin / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002210:Caprylates; D004220:Disulfides; D007328:Insulin; D012065:Relaxin; D003545:Cysteine; C031492:octanoic acid