1fb9
EFFECTS OF S-SULFONATION ON THE SOLUTION STRUCTURE OF SALMON CALCITONIN
OverviewOverview
Salmon calcitonin S-sulfonated analog (abbreviated as [S-SO(3)(-)]rsCT) was prepared by introducing two sulfonic groups into the side chains of Cys1 and Cys7 of recombinant salmon calcitonin. The hypocalcemic potency of this open-chain analog is 5500IU/mg, which is about 30% higher than that (4500IU/mg) of the wild type. The solution conformation of [S-SO(3)(-)]rsCT was studied in aqueous trifluoroethanol solution by CD, 2D-NMR spectroscopy, and distance geometry calculations. In the mixture of 60% TFE and 40% water, the peptide assumes an amphipathic alpha-helix in the region of residues 4-22, which is one turn longer than that of the native sCT. The structural feature analysis of the peptide revealed the presence of hydrophobic surface composed of five hydrophobic side chains of residues Leu4, Leu9, Leu12, Leu16, and Leu19, and a network of salt-bridges that consisted of a tetrad of oppositely charged side chains (Cys7-SO(3)(-)-Lys11(+)-Glu15(-)-Lys18(+)). The multiple salt bridges resulted in the stabilization of the longer amphipathic alpha-helix. Meanwhile, the higher hypocalcemic potency of the peptide could be attributed to the array of hydrophobic side chains of five leucine residues of the amphipathic alpha-helix.
About this StructureAbout this Structure
1FB9 is a Single protein structure of sequence from Oncorhynchus gorbuscha. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure and biological activity of recombinant salmon calcitonin S-sulfonated analog., Wang Y, Dou H, Cao C, Zhang N, Ma J, Mao J, Wu H, Biochem Biophys Res Commun. 2003 Jun 27;306(2):582-9. PMID:12804605 Page seeded by OCA on Fri May 2 16:07:35 2008