Structural highlights
Function
[CXKG_CONGE] Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin is selective for the NR2B/GRIN2B subunit. Induces sleep-like symptoms in young mice and hyperactivity in older mice.[1]
Publication Abstract from PubMed
Conantokin G is a gamma-carboxyglutamic acid-containing conotoxin from the venom of the marine cone snail Conus geographus. The 17-residue peptide, which contains five gamma-carboxyglutamic acid (Gla) residues and an amidated C-terminal asparagine amide, was synthesized chemically in a form identical to the natural conantokin G. To gain insight into the role of gamma-carboxyglutamic acid in the structure of this peptide, we determined the three-dimensional structure of conantokin G by 1H NMR and compared its structure to other conotoxins and to the gamma-carboxyglutamic acid-containing regions of the vitamin K-dependent blood-clotting proteins. Complete resonance assignments were made by two-dimensional 1H NMR spectroscopy in the absence of metal ions. NOE cross-peaks d(alphaN), d(NN), and d(betaN) provided interproton distance information, and vicinal spin-spin coupling constants 3J(HN alpha) were used to calculate phi torsion angles. Distance geometry and simulated annealing methods were used to derive 20 convergent structures from a set of 227 interproton distance restraints and 13 torsion angle measurements. The backbone rmsd to the geometric average for 20 final structures is 0.8 +/- 0.1 A. Conantokin G consists of a structured region commencing at Gla 3 and extending through arginine 13. This structure includes a partial loop centered around Gla 3 and Gla 4, a distorted type I turn between glutamine 6 and glutamine 9, and two type I turns involving Gla 10, leucine 11, and isoleucine 12 and arginine 13. Together, these two turns define approximately 1.6 turns of a distorted 3(10) helix. The observed structure possesses structural elements similar to those seen in the disulfide-linked conotoxins.
Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer.,Rigby AC, Baleja JD, Furie BC, Furie B Biochemistry. 1997 Jun 10;36(23):6906-14. PMID:9188685[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Olivera BM, Rivier J, Clark C, Ramilo CA, Corpuz GP, Abogadie FC, Mena EE, Woodward SR, Hillyard DR, Cruz LJ. Diversity of Conus neuropeptides. Science. 1990 Jul 20;249(4966):257-63. PMID:2165278
- ↑ Rigby AC, Baleja JD, Furie BC, Furie B. Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer. Biochemistry. 1997 Jun 10;36(23):6906-14. PMID:9188685 doi:10.1021/bi970321w
