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.
Büllesbach
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Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, USA.
Schwabe
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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