ANT_AMAPH
ID ANT_AMAPH Reviewed; 10 AA.
AC P0CU56;
DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 1.
DT 11-DEC-2019, entry version 3.
DE RecName: Full=Antamanide {ECO:0000303|PubMed:4966639};
DE Short=ANT {ECO:0000303|PubMed:4966639};
OS Amanita phalloides (Death cap).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Amanitaceae; Amanita.
OX NCBI_TaxID=67723;
RN [1]
RP PROTEIN SEQUENCE, AND FUNCTION.
RX PubMed=4966639; DOI=10.1002/anie.196802041;
RA Wieland T.;
RT "The discovery, isolation, elucidation of structure, and synthesis of
RT antamanide.";
RL Angew. Chem. Int. Ed. 7:204-208(1968).
RN [2]
RP FUNCTION.
RX PubMed=2442001; DOI=10.1016/0014-2999(87)90332-3;
RA Raymond G., Potreau D., Cognard C., Jahn W., Wieland T.;
RT "Antamanide antagonizes the phalloidin-induced negative inotropic effect
RT and blocks voltage dependently the fast outward K+ current in voltage-
RT clamped frog muscle fibres.";
RL Eur. J. Pharmacol. 138:21-27(1987).
RN [3]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=2033005; DOI=10.1152/jappl.1991.70.3.1364;
RA Welbourn R., Goldman G., Kobzik L., Valeri C.R., Hechtman H.B., Shepro D.;
RT "Attenuation of IL-2-induced multisystem organ edema by phalloidin and
RT antamanide.";
RL J. Appl. Physiol. 70:1364-1368(1991).
RN [4]
RP FUNCTION.
RX PubMed=1494502; DOI=10.1016/0196-9781(92)90034-z;
RA Siemion I.Z., Pedyczak A., Trojnar J., Zimecki M., Wieczorek Z.;
RT "Immunosuppressive activity of antamanide and some of its analogues.";
RL Peptides 13:1233-1237(1992).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF PHE-1 AND PHE-8.
RX PubMed=21297983; DOI=10.1371/journal.pone.0016280;
RA Azzolin L., Antolini N., Calderan A., Ruzza P., Sciacovelli M., Marin O.,
RA Mammi S., Bernardi P., Rasola A.;
RT "Antamanide, a derivative of Amanita phalloides, is a novel inhibitor of
RT the mitochondrial permeability transition pore.";
RL PLoS ONE 6:E16280-E16280(2011).
RN [6]
RP CYCLIZATION.
RX PubMed=28866879; DOI=10.1021/acssynbio.7b00264;
RA Sgambelluri R.M., Smith M.O., Walton J.D.;
RT "Versatility of prolyl oligopeptidase B in peptide macrocyclization.";
RL ACS Synth. Biol. 7:145-152(2018).
CC -!- FUNCTION: Cyclic decapeptide that belongs to the MSDIN-like toxin
CC family responsible for a large number of food poisoning cases and
CC deaths (PubMed:4966639). Counteracts the lethal action of the Amanita
CC toxins phalloidin and alpha-amanatin if administered before, or
CC simultaneously with, the poisons (PubMed:4966639, PubMed:2442001). Acts
CC probably through competitive antagonism (PubMed:2442001). Its
CC concentration in the fungus is, however, so low that the toxic action
CC of the latter predominates (PubMed:4966639). Shows immunosuppressive
CC activity, probably through the inhibition of the action of interleukin-
CC 1 and interleukin-2 (PubMed:2033005, PubMed:1494502). Antamanide
CC inhibits the mitochondrial permeability transition pore, a central
CC effector of cell death induction, by targeting the pore regulator
CC cyclophilin D (PubMed:21297983). {ECO:0000269|PubMed:1494502,
CC ECO:0000269|PubMed:2033005, ECO:0000269|PubMed:21297983,
CC ECO:0000269|PubMed:4966639}.
CC -!- PTM: Processed by the macrocyclase-peptidase enzyme POPB to yield a
CC cyclic decapeptide (PubMed:28866879). POPB first removes 10 residues
CC from the N-terminus (By similarity). Conformational trapping of the
CC remaining peptide forces the enzyme to release this intermediate rather
CC than proceed to macrocyclization (By similarity). The enzyme rebinds
CC the remaining peptide in a different conformation and catalyzes
CC macrocyclization of the N-terminal 10 residues (PubMed:28866879).
CC {ECO:0000250|UniProtKB:A0A067SLB9, ECO:0000269|PubMed:28866879}.
CC -!- BIOTECHNOLOGY: Antamanide reduces multiorgan injury induced by IL-2,
CC such as lung, hart and kidney edema; but does not have the toxicity of
CC related cyclopeptides such as phalloidin (PubMed:2033005).
CC {ECO:0000269|PubMed:2033005}.
CC -!- SIMILARITY: Belongs to the MSDIN fungal toxin family. {ECO:0000305}.
CC -!- CAUTION: The linear sequence initially published does not reflect the
CC actual order of residues as encoded by the genome which begins with a
CC Phe residue and ends with a Pro residue, the latter being important for
CC cyclization (PubMed:4966639). {ECO:0000305|PubMed:4966639}.
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PE 1: Evidence at protein level;
KW Direct protein sequencing.
FT PEPTIDE 1..10
FT /note="Antamanide"
FT /evidence="ECO:0000305|PubMed:4966639"
FT /id="PRO_0000443776"
FT CROSSLNK 1..10
FT /note="Cyclopeptide (Phe-Pro)"
FT /evidence="ECO:0000269|PubMed:28866879,
FT ECO:0000269|PubMed:4966639"
FT MUTAGEN 1
FT /note="F->G,Y: Impairs the inhibition of the mitochondrial
FT permeability transition pore."
FT /evidence="ECO:0000269|PubMed:21297983"
FT MUTAGEN 8
FT /note="F->G: Impairs the inhibition of the mitochondrial
FT permeability transition pore."
FT /evidence="ECO:0000269|PubMed:21297983"
SQ SEQUENCE 10 AA; 1165 MW; CFFFB7C9CDC77772 CRC64;
FFVPPAFFPP
