1FB9

EFFECTS OF S-SULFONATION ON THE SOLUTION STRUCTURE OF SALMON CALCITONIN

Summary for 1FB9

• Entry DOI: 10.2210/pdb1fb9/pdb
• Related: 1BKU 1BYV 1BZB
• Descriptor: CALCITONIN ANALOGUE (1 entity in total)
• Functional Keywords: alpha helix, signaling protein
• Biological source: Oncorhynchus gorbuscha (pink salmon)
• Total number of polymer chains: 1
• Total formula weight: 3597.02

Authors

Wu, H.,Mao, J.,Wang, Y.,Dou, H. (deposition date: 2000-07-14, release date: 2003-07-01, Last modification date: 2018-06-27)

Primary citation

Wang, Y.,Dou, H.,Cao, C.,Zhang, N.,Ma, J.,Mao, J.,Wu, H.
Solution structure and biological activity of recombinant salmon calcitonin S-sulfonated analog
Biochem.Biophys.Res.Commun., 306:582-589, 2003

PubMed Abstract: 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.

PubMed: 12804605
DOI: 10.1016/S0006-291X(03)01028-3

Experimental method

SOLUTION NMR