BIB11_SICTE
ID BIB11_SICTE Reviewed; 279 AA.
AC A0A0D4WV12;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2015, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Dermonecrotic toxin StSicTox-betaIB1i {ECO:0000303|PubMed:25752604};
DE EC=4.6.1.- {ECO:0000269|PubMed:25752604};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D;
DE Short=SMD;
DE Short=SMase D;
DE Short=Sphingomyelinase D;
OS Sicarius terrosus (Cave spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Sicarius.
OX NCBI_TaxID=571544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) IN
RP COMPLEX WITH MAGNESIUM, DISULFIDE BOND, CATALYTIC ACTIVITY, FUNCTION,
RP MUTAGENESIS OF ASN-96; GLU-135 AND GLY-192, AND COFACTOR.
RC TISSUE=Venom gland;
RX PubMed=25752604; DOI=10.1074/jbc.m115.636951;
RA Lajoie D.M., Roberts S.A., Zobel-Thropp P.A., Delahaye J.L., Bandarian V.,
RA Binford G.J., Cordes M.H.;
RT "Variable substrate preference among phospholipase D toxins from Sicariid
RT spiders.";
RL J. Biol. Chem. 290:10994-11007(2015).
RN [2]
RP IMPORTANT SITES FOR ACTIVITY ON SPHINGOMYELIN.
RX PubMed=16480957; DOI=10.1016/j.bbrc.2006.01.123;
RA Murakami M.T., Fernandes-Pedrosa M.F., de Andrade S.A., Gabdoulkhakov A.,
RA Betzel C., Tambourgi D.V., Arni R.K.;
RT "Structural insights into the catalytic mechanism of sphingomyelinases D
RT and evolutionary relationship to glycerophosphodiester
RT phosphodiesterases.";
RL Biochem. Biophys. Res. Commun. 342:323-329(2006).
CC -!- FUNCTION: Dermonecrotic toxins cleave the phosphodiester linkage
CC between the phosphate and headgroup of certain phospholipids
CC (sphingolipid and lysolipid substrates), forming an alcohol (often
CC choline) and a cyclic phosphate (PubMed:25752604). This toxin acts on
CC lysophosphatidylethanolamine (LPE) and ceramide phosphoethanolamine
CC (CPE) with high activity (PubMed:25752604). This toxin acts on
CC sphingomyelin (SM) with very low activity and is not active on
CC lysophosphatidylserine (LPS), lysophosphatidylcholine (LPC) and
CC lysophosphatidylglycerol (LPG) (PubMed:25752604). It acts by
CC transphosphatidylation, releasing exclusively cyclic phosphate as
CC second products (PubMed:25752604). It is not surprising that spider
CC toxins have affinity for ethanolamine-containing sphingolipids since
CC they are common in insect prey (PubMed:25752604). Induces
CC dermonecrosis, hemolysis, increased vascular permeability, edema,
CC inflammatory response, and platelet aggregation (By similarity).
CC {ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:25752604}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-(acyl)-sphingosylphosphocholine = an N-(acyl)-sphingosyl-
CC 1,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60652,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:64583, ChEBI:CHEBI:143892;
CC Evidence={ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-hexanoyl-sphing-4-enine-1-phosphocholine = choline + N-
CC (hexanoyl)-sphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60620,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:78254, ChEBI:CHEBI:143883;
CC Evidence={ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-
CC sphingosyl-1,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60648,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:143891, ChEBI:CHEBI:143892;
CC Evidence={ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-dodecanoyl-heptadecasphing-4-enine-1-phosphoethanolamine =
CC ethanolamine + N-dodecanoyl-heptadecasphing-4-enine-1,3-cyclic
CC phosphate; Xref=Rhea:RHEA:60616, ChEBI:CHEBI:57603,
CC ChEBI:CHEBI:143864, ChEBI:CHEBI:143865;
CC Evidence={ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-
CC glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60704,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:64381, ChEBI:CHEBI:143947;
CC Evidence={ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycero-3-phosphoethanolamine = 1-
CC tetradecanoyl-sn-glycero-2,3-cyclic phosphate + ethanolamine;
CC Xref=Rhea:RHEA:60608, ChEBI:CHEBI:57603, ChEBI:CHEBI:84299,
CC ChEBI:CHEBI:143882; Evidence={ECO:0000269|PubMed:25752604};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:25752604, ECO:0000312|PDB:4Q6X};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:25752604,
CC ECO:0000312|PDB:4Q6X};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25752604}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:25752604}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class II
CC subfamily. Class IIb sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: The most common activity assay for dermonecrotic toxins
CC detects enzymatic activity by monitoring choline release from
CC substrate. Liberation of choline from sphingomyelin (SM) or
CC lysophosphatidylcholine (LPC) is commonly assumed to result from
CC substrate hydrolysis, giving either ceramide-1-phosphate (C1P) or
CC lysophosphatidic acid (LPA), respectively, as a second product.
CC However, two studies from Lajoie and colleagues (2013 and 2015) report
CC the observation of exclusive formation of cyclic phosphate products as
CC second products, resulting from intramolecular transphosphatidylation.
CC Cyclic phosphates have vastly different biological properties from
CC their monoester counterparts, and they may be relevant to the pathology
CC of brown spider envenomation. {ECO:0000250|UniProtKB:Q4ZFU2,
CC ECO:0000269|PubMed:25752604}.
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DR EMBL; KM884813; AJV88488.1; -; mRNA.
DR PDB; 4Q6X; X-ray; 2.14 A; A=1-279.
DR PDBsum; 4Q6X; -.
DR AlphaFoldDB; A0A0D4WV12; -.
DR SMR; A0A0D4WV12; -.
DR SwissLipids; SLP:000001962; -.
DR BRENDA; 3.1.4.4; 16541.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.190; -; 1.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR SUPFAM; SSF51695; SSF51695; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytolysis; Dermonecrotic toxin; Disulfide bond; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Toxin; Zymogen.
FT CHAIN 1..279
FT /note="Dermonecrotic toxin StSicTox-betaIB1i"
FT /id="PRO_0000447765"
FT ACT_SITE 12
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 48
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 32
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:25752604,
FT ECO:0000312|PDB:4Q6X"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:25752604,
FT ECO:0000312|PDB:4Q6X"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:25752604,
FT ECO:0000312|PDB:4Q6X"
FT SITE 96
FT /note="May prevent sphingomyelin recognition"
FT /evidence="ECO:0000305|PubMed:16480957"
FT SITE 135
FT /note="May prevent sphingomyelin recognition"
FT /evidence="ECO:0000305|PubMed:16480957"
FT DISULFID 52..58
FT /evidence="ECO:0000269|PubMed:25752604,
FT ECO:0000312|PDB:4Q6X"
FT DISULFID 54..198
FT /evidence="ECO:0000269|PubMed:25752604,
FT ECO:0000312|PDB:4Q6X"
FT MUTAGEN 96
FT /note="N->S: Has limited impact on substrate specificity
FT and does not alter it qualitatively; when associated with
FT P-135."
FT /evidence="ECO:0000269|PubMed:25752604"
FT MUTAGEN 135
FT /note="E->P: Has limited impact on substrate specificity
FT and does not alter it qualitatively; when associated with
FT S-192. Has limited impact on substrate specificity and does
FT not alter it qualitatively; when associated with S-96."
FT /evidence="ECO:0000269|PubMed:25752604"
FT MUTAGEN 192
FT /note="G->S: Has limited impact on substrate specificity
FT and does not alter it qualitatively; when associated with
FT P-135."
FT /evidence="ECO:0000269|PubMed:25752604"
FT STRAND 4..12
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 29..37
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 64..74
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 100..117
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 141..152
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 173..182
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 187..194
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 204..214
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 244..249
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 251..258
FT /evidence="ECO:0007829|PDB:4Q6X"
FT HELIX 261..264
FT /evidence="ECO:0007829|PDB:4Q6X"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:4Q6X"
SQ SEQUENCE 279 AA; 31815 MW; 6A715A8DCA641759 CRC64;
GDSRRPIWNI AHMVNDLDLV DEYLDDGANS LELDVEFSKS GTALRTYHGV PCDCFRSCTR
SEKFSKYLDY IRQLTTPGNS KFRSRLILLV LDLKLNPLSS SAAYNAGADV ARNLLDNYWQ
RGDSKARAYI VLSLETIAGA EFITGFKDTM KKEGFDEKYY DKIGWDFSGN EDLGKIRDVL
ESHGIREHIW QGDGITNCLP RDDNRLKQAI SRRYSPTYVY ADKVYTWSID KESSIENALR
LGVDGVMTNY PARVISVLGE REFSGKLRLA TYDDNPWEK
