5DZ5: Crystal Structure Of Dendroaspis Polylepis Mambalgin-1 Wild-type In P41212 Space Group

Citation:
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.
PDB ID: 5DZ5Download
MMDB ID: 135193
PDB Deposition Date: 2015/9/25
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 5DZ5: tetrameric; determined by author and by software (PISA)
Molecular Components in 5DZ5
Label Count Molecule
Proteins (4 molecules)
4
Mambalgin-1
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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