8CJS
JzTx-34 toxin peptide W31A mutant
Summary for 8CJS
| Entry DOI | 10.2210/pdb8cjs/pdb |
| Related | 8CIQ |
| NMR Information | BMRB: 34794 |
| Descriptor | Mu-theraphotoxin-Cg1a (1 entity in total) |
| Functional Keywords | toxin jztx-34 wild type peptide toxin hnav1.1 channel sodium channel, toxin |
| Biological source | Chilobrachys |
| Total number of polymer chains | 1 |
| Total formula weight | 4048.68 |
| Authors | Landon, C.,Meudal, H. (deposition date: 2023-02-13, release date: 2023-07-26, Last modification date: 2024-10-23) |
| Primary citation | Lopez, L.,De Waard, S.,Meudal, H.,Caumes, C.,Khakh, K.,Peigneur, S.,Oliveira-Mendes, B.,Lin, S.,De Waele, J.,Montnach, J.,Cestele, S.,Tessier, A.,Johnson, J.P.,Mantegazza, M.,Tytgat, J.,Cohen, C.,Beroud, R.,Bosmans, F.,Landon, C.,De Waard, M. Structure-function relationship of new peptides activating human Na v 1.1. Biomed Pharmacother, 165:115173-115173, 2023 Cited by PubMed Abstract: Na1.1 is an important pharmacological target as this voltage-gated sodium channel is involved in neurological and cardiac syndromes. Channel activators are actively sought to try to compensate for haploinsufficiency in several of these pathologies. Herein we used a natural source of new peptide compounds active on ion channels and screened for drugs capable to inhibit channel inactivation as a way to compensate for decreased channel function. We discovered that JzTx-34 is highly active on Na1.1 and subsequently performed a full structure-activity relationship investigation to identify its pharmacophore. These experiments will help interpret the mechanism of action of this and formerly identified peptides as well as the future identification of new peptides. We also reveal structural determinants that make natural ICK peptides active against Na1.1 challenging to synthesize. Altogether, the knowledge gained by this study will help facilitate the discovery and development of new compounds active on this critical ion channel target. PubMed: 37453200DOI: 10.1016/j.biopha.2023.115173 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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