7TVQ

Structure of the globular isoform of the novel conotoxin PnID derived from Conus pennaceus

Replaces:  5T6TReplaces:  5T6V

Summary for 7TVQ

• Entry DOI: 10.2210/pdb7tvq/pdb
• NMR Information: BMRB: 30991
• Descriptor: Chi-conotoxin-like PnMRCL-013 (1 entity in total)
• Functional Keywords: venom peptide, toxin, conotoxin
• Biological source: Conus pennaceus
• Total number of polymer chains: 1
• Total formula weight: 1321.64

Authors

Loening, N.M.,Espiritu, M.J. (deposition date: 2022-02-05, release date: 2023-01-25, Last modification date: 2023-03-08)

Primary citation

Espiritu, M.J.,Taylor, J.K.,Sugai, C.K.,Thapa, P.,Loening, N.M.,Gusman, E.,Baoanan, Z.G.,Baumann, M.H.,Bingham, J.P.
Characterization of the Native Disulfide Isomers of the Novel chi-Conotoxin PnID: Implications for Further Increasing Conotoxin Diversity.
Mar Drugs, 21:-, 2023

PubMed Abstract: χ-Conotoxins are known for their ability to selectively inhibit norepinephrine transporters, an ability that makes them potential leads for treating various neurological disorders, including neuropathic pain. PnID, a peptide isolated from the venom of , shares high sequence homology with previously characterized χ-conotoxins. Whereas previously reported χ-conotoxins seem to only have a single native disulfide bonding pattern, PnID has three native isomers due to the formation of different disulfide bond patterns during its maturation in the venom duct. In this study, the disulfide connectivity and three-dimensional structure of these disulfide isomers were explored using regioselective synthesis, chromatographic coelution, and solution-state nuclear magnetic resonance spectroscopy. Of the native isomers, only the isomer with a ribbon disulfide configuration showed pharmacological activity similar to other χ-conotoxins. This isomer inhibited the rat norepinephrine transporter (IC = 10 ± 2 µM) and has the most structural similarity to previously characterized χ-conotoxins. In contrast, the globular isoform of PnID showed more than ten times less activity against this transporter and the beaded isoform did not display any measurable biological activity. This study is the first report of the pharmacological and structural characterization of an χ-conotoxin from a species other than and is the first report of the existence of natively-formed conotoxin isomers.

PubMed: 36827103
DOI: 10.3390/md21020061

Experimental method

SOLUTION NMR