1R9I

NMR Solution Structure of PIIIA toxin, NMR, 20 structures

Summary for 1R9I

• Entry DOI: 10.2210/pdb1r9i/pdb
• NMR Information: BMRB: 6027
• Descriptor: Mu-conotoxin PIIIA (1 entity in total)
• Functional Keywords: conotoxin, cysteine knot, toxin
• Biological source: Conus purpurascens
• Total number of polymer chains: 1
• Total formula weight: 2618.16

Authors

Nielsen, K.J.,Watson, M.,Adams, D.J.,Hammarstrom, A.K.,Gage, P.W.,Hill, J.M.,Craik, D.J.,Thomas, L.,Adams, D.,Alewood, P.F.,Lewis, R.J. (deposition date: 2003-10-30, release date: 2003-11-18, Last modification date: 2019-12-25)

Primary citation

Nielsen, K.J.,Watson, M.,Adams, D.J.,Hammarstrom, A.K.,Gage, P.W.,Hill, J.M.,Craik, D.J.,Thomas, L.,Adams, D.,Alewood, P.F.,Lewis, R.J.
Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels
J.Biol.Chem., 277:27247-27255, 2002

PubMed Abstract: 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.

PubMed: 12006587
DOI: 10.1074/jbc.M201611200

Experimental method

SOLUTION NMR