5du1
Crystal structure of Dendroaspis polylepis mambalgin-1 wild-type in P21 space group.Crystal structure of Dendroaspis polylepis mambalgin-1 wild-type in P21 space group.
Structural highlights
FunctionPublication Abstract from PubMedMambalgins 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 3D 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 Phe27, Leu32 and Leu34 residues. Moreover, proximity between Leu32 in mambalgin-1 and Phe350 in rASIC1a was proposed from double-mutant cycle analysis. These data give 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. Mambalgin-1 pain-relieving peptide: stepwise solid-phase synthesis, crystal structure and functional domain for acid-sensing ion channel 1a inhibition.,Mourier G, Salinas M, Kessler P, Stura EA, Leblanc M, Tepshi L, Besson T, Diochot S, Baron A, Douguet D, Lingueglia E, Servent D J Biol Chem. 2015 Dec 17. pii: jbc.M115.702373. PMID:26680001[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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