5DO6
Crystal structure of Dendroaspis polylepis venom mambalgin-1 T23A mutant
Summary for 5DO6
| Entry DOI | 10.2210/pdb5do6/pdb |
| Related | 2MFA 2MJY |
| Descriptor | Mambalgin-1, IODIDE ION, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | toxin, acid sensing ion channels, pain suppression drug, elapid venom polypeptide |
| Biological source | Dendroaspis polylepis polylepis (Black mamba) |
| Cellular location | Secreted : P0DKR6 |
| Total number of polymer chains | 2 |
| Total formula weight | 13861.92 |
| Authors | Stura, E.A.,Tepshi, L.,Kessler, P.,Gilles, M.,Servent, D. (deposition date: 2015-09-10, release date: 2015-12-30, Last modification date: 2024-10-23) |
| Primary citation | Mourier, G.,Salinas, M.,Kessler, P.,Stura, E.A.,Leblanc, M.,Tepshi, L.,Besson, T.,Diochot, S.,Baron, A.,Douguet, D.,Lingueglia, E.,Servent, D. Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition. J.Biol.Chem., 291:2616-2629, 2016 Cited by PubMed Abstract: Mambalgins are peptides isolated from mamba venom that specifically inhibit a set of acid-sensing ion channels (ASICs) to relieve pain. We show here the first full stepwise solid phase peptide synthesis of mambalgin-1 and confirm the biological activity of the synthetic toxin both in vitro and in vivo. We also report the determination of its three-dimensional crystal structure showing differences with previously described NMR structures. Finally, the functional domain by which the toxin inhibits ASIC1a channels was identified in its loop II and more precisely in the face containing Phe-27, Leu-32, and Leu-34 residues. Moreover, proximity between Leu-32 in mambalgin-1 and Phe-350 in rASIC1a was proposed from double mutant cycle analysis. These data provide information on the structure and on the pharmacophore for ASIC channel inhibition by mambalgins that could have therapeutic value against pain and probably other neurological disorders. PubMed: 26680001DOI: 10.1074/jbc.M115.702373 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.697 Å) |
Structure validation
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