1srb
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CONFORMATIONAL STUDIES ON SRTB, A NON-SELECTIVE ENDOTHELIN RECEPTOR AGONIST, AND ON IRL 1620, AN ETB RECEPTOR SPECIFIC AGONIST
OverviewOverview
1H NMR studies on the nonselective endothelin receptor agonist sarafotoxin, SRTb have identified a helix between residues Asp 8 and His 16, and a, beta-turn involving residues Cys 3 to Met 6; however, the biologically, important C-terminal five residues were found to be conformationally, variable. The average RMSD, measured for the final 43 refined structures, to the average structure over residues 1-16, was 0.78 +/- 0.18 A for the, backbone atoms and 1.39 +/- 0.22 A for all atoms. The torsion angles Cys 3, psi/Lys 4 theta, Thr 7 psi/Asp 8 theta and Gln 17 theta were identified as, sites of conformational variability. Differences were found between the, structures in the bicyclic loop region for SRTb and those published for, ET1, another nonselective receptor agonist, which may explain the observed, differences in potency of these peptides. The conformation of an ETB, receptor-specific agonist, IRL 1620, which lacks the N-terminal seven, residues and the two intrachain disulfides, was found by NMR and circular, dichroism spectroscopy to be predominantly random coil, despite the fact, that its affinity for the ETB receptor almost equals that of ET1. However, close analysis of the NMR results indicated the presence of turn-like, structures, or a nascent helix, in the part of the sequence corresponding, to the helical region in the parent peptides. These results suggest that, the helical conformation may be required for ligand binding to the ETB, receptor as well as to the ETA receptor.
About this StructureAbout this Structure
1SRB is a Single protein structure of sequence from Atractaspis microlepidota andersoni. Full crystallographic information is available from OCA.
ReferenceReference
1H NMR studies of sarafotoxin SRTb, a nonselective endothelin receptor agonist, and IRL 1620, an ETB receptor-specific agonist., Atkins AR, Martin RC, Smith R, Biochemistry. 1995 Feb 14;34(6):2026-33. PMID:7849060
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