6SAB
M-BUTX-Ptr1a (Parabuthus transvaalicus)
Summary for 6SAB
| Entry DOI | 10.2210/pdb6sab/pdb |
| NMR Information | BMRB: 34418 |
| Descriptor | M-BUTX-Ptr1a (1 entity in total) |
| Functional Keywords | screening, melanocortin receptor, gpcr, animal toxin, toxin |
| Biological source | Parabuthus transvaalicus (South African fattail scorpion) |
| Total number of polymer chains | 1 |
| Total formula weight | 3809.74 |
| Authors | Meudal, H.,Landon, C.,Delmas, A.F. (deposition date: 2019-07-16, release date: 2020-07-22, Last modification date: 2024-11-20) |
| Primary citation | Reynaud, S.,Ciolek, J.,Degueldre, M.,Saez, N.J.,Sequeira, A.F.,Duhoo, Y.,Bras, J.L.A.,Meudal, H.,Cabo Diez, M.,Fernandez Pedrosa, V.,Verdenaud, M.,Boeri, J.,Pereira Ramos, O.,Ducancel, F.,Vanden Driessche, M.,Fourmy, R.,Violette, A.,Upert, G.,Mourier, G.,Beck-Sickinger, A.G.,Morl, K.,Landon, C.,Fontes, C.M.G.A.,Minambres Herraiz, R.,Rodriguez de la Vega, R.C.,Peigneur, S.,Tytgat, J.,Quinton, L.,De Pauw, E.,Vincentelli, R.,Servent, D.,Gilles, N. A Venomics Approach Coupled to High-Throughput Toxin Production Strategies Identifies the First Venom-Derived Melanocortin Receptor Agonists. J.Med.Chem., 63:8250-8264, 2020 Cited by PubMed Abstract: Animal venoms are rich in hundreds of toxins with extraordinary biological activities. Their exploitation is difficult due to their complexity and the small quantities of venom available from most venomous species. We developed a Venomics approach combining transcriptomic and proteomic characterization of 191 species and identified 20,206 venom toxin sequences. Two complementary production strategies based on solid-phase synthesis and recombinant expression in generated a physical bank of 3597 toxins. Screened on hMC4R, this bank gave an incredible hit rate of 8%. Here, we focus on two novel toxins: N-TRTX-Preg1a, exhibiting an inhibitory cystine knot (ICK) motif, and N-BUTX-Ptr1a, a short scorpion-CSαβ structure. Neither N-TRTX-Preg1a nor N-BUTX-Ptr1a affects ion channels, the known targets of their toxin scaffolds, but binds to four melanocortin receptors with low micromolar affinities and activates the hMC1R/Gs pathway. Phylogenetically, these two toxins form new groups within their respective families and represent novel hMC1R agonists, structurally unrelated to the natural agonists. PubMed: 32602722DOI: 10.1021/acs.jmedchem.0c00485 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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