2LU6
NMR solution structure of Midi peptide designed based on m-conotoxins
Summary for 2LU6
| Entry DOI | 10.2210/pdb2lu6/pdb |
| NMR Information | BMRB: 18510 |
| Descriptor | Midi peptide designed based on m-conotoxins (1 entity in total) |
| Functional Keywords | m-conotoxin, kiiia, buiiic, de novo protein, toxin |
| Total number of polymer chains | 1 |
| Total formula weight | 1700.95 |
| Authors | Dyubankova, N.,Lescrinier, E.,Stevens, M.,Tytgat, J.,Herdewijn, P.,Peigneur, S. (deposition date: 2012-06-08, release date: 2012-06-27, Last modification date: 2024-11-06) |
| Primary citation | Stevens, M.,Peigneur, S.,Dyubankova, N.,Lescrinier, E.,Herdewijn, P.,Tytgat, J. Design of bioactive peptides from naturally occurring mu-conotoxin structures. J.Biol.Chem., 287:31382-31392, 2012 Cited by PubMed Abstract: To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Na(v)s). Na(v)s participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases. The development of subtype-selective modulators of Na(v)s remains highly important in the treatment of such disorders. In current research, a series of novel, synthetic, and bioactive compounds were designed based on two naturally occurring μ-conotoxins that target Na(v)s. The initial designed peptide contains solely 13 amino acids and was therefore named "Mini peptide." It was derived from the μ-conotoxins KIIIA and BuIIIC. Based on this Mini peptide, 10 analogues were subsequently developed, comprising 12-16 amino acids with two disulfide bridges. Following appropriate folding and mass verification, blocking effects on Na(v)s were investigated. The most promising compound established an IC(50) of 34.1 ± 0.01 nM (R2-Midi on Na(v)1.2). An NMR structure of one of our most promising compounds was determined. Surprisingly, this structure does not reveal an α-helix. We prove that it is possible to design small peptides based on known pharmacophores of μ-conotoxins without losing their potency and selectivity. These data can provide crucial material for further development of conotoxin-based therapeutics. PubMed: 22773842DOI: 10.1074/jbc.M112.375733 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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