ID   3L24_DENPO              Reviewed;          72 AA.
AC   C0HJD7;
DT   29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT   29-OCT-2014, sequence version 1.
DT   25-MAY-2022, entry version 26.
DE   RecName: Full=Alpha-elapitoxin-Dpp2d {ECO:0000303|PubMed:24867092};
DE            Short=Alpha-EPTX-Dpp2d {ECO:0000303|PubMed:24867092};
OS   Dendroaspis polylepis polylepis (Black mamba).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX   NCBI_TaxID=8620;
RN   [1]
RP   PROTEIN SEQUENCE, MASS SPECTROMETRY, FUNCTION, X-RAY CRYSTALLOGRAPHY (1.7
RP   ANGSTROMS), AMIDATION AT ARG-72, SUBCELLULAR LOCATION, AND SUBUNIT.
RC   TISSUE=Venom;
RX   PubMed=24867092; DOI=10.1021/bi5004475;
RA   Wang C.I., Reeks T., Vetter I., Vergara I., Kovtun O., Lewis R.J.,
RA   Alewood P.F., Durek T.;
RT   "Isolation and structural and pharmacological characterization of alpha-
RT   elapitoxin-Dpp2d, an amidated three finger toxin from black mamba venom.";
RL   Biochemistry 53:3758-3766(2014).
CC   -!- FUNCTION: Binds with high affinity to muscular (IC(50)=114 nM) and
CC       neuronal (alpha-7/CHRNA7) (IC(50)=58 nM) nicotinic acetylcholine
CC       receptor (nAChR) and inhibits acetylcholine from binding to the
CC       receptor, thereby impairing neuromuscular and neuronal transmission.
CC       Competitive radioligand binding assays also demonstrate that this toxin
CC       competes with epibatidine binding to the Lymnea stagnalis
CC       acetylcholine-binding protein (Ls-AChBP) (IC(50)=4.9 nM).
CC       {ECO:0000250|UniProtKB:P60615, ECO:0000269|PubMed:24867092}.
CC   -!- SUBUNIT: Monomer (predominant). {ECO:0000303|PubMed:24867092}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24867092}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:24867092}.
CC   -!- PTM: Amidation does not significantly affect toxin selectivity, since
CC       the activity profile and binding data are reminiscent of classical
CC       long-chain 3-finger toxins with a free carboxyl termini.
CC       {ECO:0000269|PubMed:24867092}.
CC   -!- MASS SPECTROMETRY: Mass=7985.33; Mass_error=0.40; Method=Electrospray;
CC       Note=Monoisotopic mass.; Evidence={ECO:0000269|PubMed:24867092};
CC   -!- MISCELLANEOUS: Does not affect alpha-3/beta-2 (CHRNA3/CHRNB2) and
CC       alpha-3/beta-4 (CHRNA3/CHRNB4) nAChRs at 1 uM concentrations.
CC       {ECO:0000269|PubMed:24867092}.
CC   -!- SIMILARITY: Belongs to the snake three-finger toxin family. Long-chain
CC       subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.
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DR   PDB; 4LFT; X-ray; 1.70 A; A/B=1-72.
DR   PDBsum; 4LFT; -.
DR   AlphaFoldDB; C0HJD7; -.
DR   SMR; C0HJD7; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   CDD; cd00206; snake_toxin; 1.
DR   Gene3D; 2.10.60.10; -; 1.
DR   InterPro; IPR003571; Snake_3FTx.
DR   InterPro; IPR045860; Snake_toxin-like_sf.
DR   InterPro; IPR018354; Snake_toxin_con_site.
DR   SUPFAM; SSF57302; SSF57302; 1.
DR   PROSITE; PS00272; SNAKE_TOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Postsynaptic neurotoxin; Secreted; Toxin.
FT   CHAIN           1..72
FT                   /note="Alpha-elapitoxin-Dpp2d"
FT                   /evidence="ECO:0000269|PubMed:24867092"
FT                   /id="PRO_0000430751"
FT   MOD_RES         72
FT                   /note="Arginine amide"
FT                   /evidence="ECO:0000269|PubMed:24867092"
FT   DISULFID        3..21
FT                   /evidence="ECO:0000269|PubMed:24867092,
FT                   ECO:0000312|PDB:4LFT"
FT   DISULFID        14..42
FT                   /evidence="ECO:0000269|PubMed:24867092,
FT                   ECO:0000312|PDB:4LFT"
FT   DISULFID        27..31
FT                   /evidence="ECO:0000269|PubMed:24867092,
FT                   ECO:0000312|PDB:4LFT"
FT   DISULFID        46..57
FT                   /evidence="ECO:0000269|PubMed:24867092,
FT                   ECO:0000312|PDB:4LFT"
FT   DISULFID        58..63
FT                   /evidence="ECO:0000269|PubMed:24867092,
FT                   ECO:0000312|PDB:4LFT"
FT   STRAND          20..26
FT                   /evidence="ECO:0007829|PDB:4LFT"
FT   HELIX           31..34
FT                   /evidence="ECO:0007829|PDB:4LFT"
FT   STRAND          37..45
FT                   /evidence="ECO:0007829|PDB:4LFT"
FT   STRAND          54..58
FT                   /evidence="ECO:0007829|PDB:4LFT"
SQ   SEQUENCE   72 AA;  8002 MW;  849151F4633E3F5F CRC64;
     RTCNKTFSDQ SKICPPGENI CYTKTWCDAF CSQRGKRVEL GCAATCPKVK AGVEIKCCST
     DNCNKFQFGK PR