1r9i | pdb_00001r9i
NMR Solution Structure of PIIIA toxin, NMR, 20 structures
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Overview
Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels, (VSSCs). Synthetic forms of mu-conotoxins PIIIA and PIIIA-(2-22) were, found to inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little, effect on TTX-resistant VSSC current in sensory ganglion neurons. In rat, brain neurons, these peptides preferentially inhibited the persistent over, the transient VSSC current. Radioligand binding assays revealed that, PIIIA, PIIIA-(2-22), and mu-conotoxins GIIIB discriminated among, TTX-sensitive VSSCs in rat brain, that these and GIIIC discriminated among, the corresponding VSSCs in human brain, and GIIIA had low affinity for, neuronal VSSCs. (1)H NMR studies found that PIIIA adopts two conformations, in solution due to cis/trans isomerization at hydroxyproline 8. The major, trans conformation results in a three-dimensional structure that is, significantly different from the previously identified conformation of, mu-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle, VSSCs. Comparison of the structures and activity of PIIIA to, muscle-selective mu-conotoxins provides an insight into the structural, requirements for inhibition of different TTX-sensitive sodium channels by, mu-conotoxins.
About this Structure
1R9I is a Single protein structure of sequence from Conus purpurascens. Full crystallographic information is available from OCA.
Reference
Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels., Nielsen KJ, Watson M, Adams DJ, Hammarstrom AK, Gage PW, Hill JM, Craik DJ, Thomas L, Adams D, Alewood PF, Lewis RJ, J Biol Chem. 2002 Jul 26;277(30):27247-55. Epub 2002 May 2. PMID:12006587
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