PA2B_VIPAE
ID PA2B_VIPAE Reviewed; 122 AA.
AC P14420;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Basic phospholipase A2 vipoxin B chain;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE AltName: Full=Vipoxin toxic component;
OS Vipera ammodytes meridionalis (Eastern sand viper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Vipera.
OX NCBI_TaxID=73841;
RN [1]
RP PROTEIN SEQUENCE.
RC STRAIN=Bulgarian; TISSUE=Venom;
RX PubMed=3606821; DOI=10.1515/bchm3.1987.368.1.343;
RA Mancheva I., Kleinschmidt T., Aleksiev B., Braunitzer G.;
RT "Sequence homology between phospholipase and its inhibitor in snake venom.
RT The primary structure of phospholipase A2 of vipoxin from the venom of the
RT Bulgarian viper (Vipera ammodytes ammodytes, Serpentes).";
RL Biol. Chem. Hoppe-Seyler 368:343-352(1987).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND LETHAL DOSES.
RC TISSUE=Venom;
RX PubMed=23554559; DOI=10.2478/v10102-012-0028-z;
RA Atanasov V.N., Stoykova S., Goranova Y., Mitewa M., Petrova S.;
RT "Acute toxicity of vipoxin and its components: is the acidic component an
RT 'inhibitor' of PLA2 toxicity?";
RL Interdiscip. Toxicol. 5:169-172(2012).
RN [3]
RP FUNCTION OF THE MONOMER.
RX PubMed=24678250; DOI=10.2478/intox-2013-0021;
RA Stoykova S., Goranova Y., Pantcheva I., Atanasov V., Danchev D.,
RA Petrova S.;
RT "Hemolytic activity and platelet aggregation inhibitory effect of vipoxin's
RT basic sPLA2 subunit.";
RL Interdiscip. Toxicol. 6:136-140(2013).
RN [4]
RP CRYSTALLIZATION.
RC TISSUE=Venom;
RX PubMed=8445639; DOI=10.1006/jmbi.1993.1109;
RA Devedjiev Y., Atanasov B., Mancheva I., Aleksiev B.;
RT "Crystals of phospholipase A2 inhibitor. The non-toxic component of vipoxin
RT from the venom of Bulgarian viper (Vipera ammodytes).";
RL J. Mol. Biol. 229:1147-1149(1993).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RC TISSUE=Venom;
RX PubMed=8510159; DOI=10.1006/jmbi.1993.1297;
RA Betzel C., Visanji M., Wilson K.S., Genov N., Mancheva I., Aleksiev B.,
RA Singh T.P.;
RT "Crystallization and preliminary X-ray analysis of vipoxin, a complex
RT between a toxic phospholipase A2 and its natural polypeptide inhibitor.";
RL J. Mol. Biol. 231:498-500(1993).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH VIPOXIN A CHAIN, AND
RP DISULFIDE BONDS.
RX PubMed=9276469; DOI=10.1016/s0014-5793(97)00853-3;
RA Perbandt M., Wilson J.C., Eschenburg S., Mancheva I., Aleksiev B.,
RA Genov N., Willingmann P., Weber W., Singh T.P., Betzel C.;
RT "Crystal structure of vipoxin at 2.0 A: an example of regulation of a toxic
RT function generated by molecular evolution.";
RL FEBS Lett. 412:573-577(1997).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH VIPOXIN A CHAIN, AND
RP DISULFIDE BONDS.
RX PubMed=11679719; DOI=10.1107/s0907444901013543;
RA Banumathi S., Rajashankar K.R., Notzel C., Aleksiev B., Singh T.P.,
RA Genov N., Betzel C.;
RT "Structure of the neurotoxic complex vipoxin at 1.4 A resolution.";
RL Acta Crystallogr. D 57:1552-1559(2001).
CC -!- FUNCTION: Heterodimer: postsynaptic neurotoxin.
CC -!- FUNCTION: Monomer: snake venom phospholipase A2 (PLA2) that shows
CC hemolytic activity and inhibition of platelet aggregation. The
CC hemolytic activity occurs only in presence of fatty acids (unsaturated
CC fatty acids facilitate induce a strong hemolytic activity, whereas
CC saturated fatty acids induce a slight activity). The inhibition of
CC platelet aggregation is almost maximal when aggregation is induced by
CC collagen, and arachidonic acid, whereas it is only of 30% when the
CC aggregation is induced by ADP. PLA2 catalyzes the calcium-dependent
CC hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10035, ECO:0000255|PROSITE-
CC ProRule:PRU10036};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P14418};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250|UniProtKB:P14418};
CC -!- SUBUNIT: Heterodimer of A (AC P04084) and B chains; non-covalently
CC linked. The A chain (acidic) is non-toxic, and increases the toxicity
CC of the B chain (basic). The A chain may act as factor stabilizing the
CC complex structure and hence retaining its toxicity by preventing non-
CC specific binding. Upon binding to the target membranes the A chain is
CC postulated to dissociate. {ECO:0000269|PubMed:11679719,
CC ECO:0000269|PubMed:23554559, ECO:0000269|PubMed:9276469}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: Heterodimer: LD(50) is 0.7-1.2 mg/kg by intraperitoneal
CC injection into mice and 0.9-1.3 mg/kg by intravenous injection into
CC mice. {ECO:0000269|PubMed:23554559}.
CC -!- TOXIC DOSE: Heterodimer: LD(50) is 0.9-1.3 mg/kg by intravenous
CC injection into mice. {ECO:0000269|PubMed:23554559}.
CC -!- TOXIC DOSE: Monomer: LD(50) is 10-13 mg/kg by intraperitoneal injection
CC into mice. {ECO:0000269|PubMed:23554559}.
CC -!- TOXIC DOSE: Monomer: LD(50) is 2.2-3.0 mg/kg by intravenous injection
CC into mice. {ECO:0000269|PubMed:23554559}.
CC -!- MISCELLANEOUS: The B chain (not complexed with the A chain) does not
CC induce neurotoxic symptoms, hemorrhage, organ injuries and other
CC macroscopic changes. {ECO:0000305|PubMed:23554559}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: The acidic chain was originally postulated to act as an
CC inhibitor of the basic chain. {ECO:0000305}.
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DR PIR; A29290; A29290.
DR PDB; 1AOK; X-ray; 2.00 A; B=1-122.
DR PDB; 1JLT; X-ray; 1.40 A; B=1-122.
DR PDB; 1RGB; X-ray; 3.30 A; A/B/K/L=1-122.
DR PDBsum; 1AOK; -.
DR PDBsum; 1JLT; -.
DR PDBsum; 1RGB; -.
DR AlphaFoldDB; P14420; -.
DR SMR; P14420; -.
DR MINT; P14420; -.
DR EvolutionaryTrace; P14420; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR CDD; cd00125; PLA2c; 1.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR033112; PLipase_A2_Asp_AS.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR InterPro; IPR033113; PLipase_A2_His_AS.
DR PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR PRINTS; PR00389; PHPHLIPASEA2.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00119; PA2_ASP; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cytolysis; Direct protein sequencing;
KW Disulfide bond; Hemolysis; Hemostasis impairing toxin; Hydrolase;
KW Lipid degradation; Lipid metabolism; Metal-binding; Neurotoxin;
KW Platelet aggregation inhibiting toxin; Postsynaptic neurotoxin; Secreted;
KW Toxin.
FT CHAIN 1..122
FT /note="Basic phospholipase A2 vipoxin B chain"
FT /id="PRO_0000161712"
FT ACT_SITE 47
FT /evidence="ECO:0000305|PubMed:9276469"
FT ACT_SITE 89
FT /evidence="ECO:0000305|PubMed:9276469"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 29
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 48
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT DISULFID 26..115
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT DISULFID 49..122
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:11679719,
FT ECO:0000269|PubMed:9276469, ECO:0007744|PDB:1AOK,
FT ECO:0007744|PDB:1JLT"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:1JLT"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:1JLT"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1JLT"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1JLT"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1JLT"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:1JLT"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:1JLT"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:1JLT"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1JLT"
FT HELIX 81..98
FT /evidence="ECO:0007829|PDB:1JLT"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:1JLT"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:1JLT"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:1JLT"
SQ SEQUENCE 122 AA; 13828 MW; 94438F9F1285FC7D CRC64;
NLFQFAKMIN GKLGAFSVWN YISYGCYCGW GGQGTPKDAT DRCCFVHDCC YGRVRGCNPK
LAIYSYSFKK GNIVCGKNNG CLRDICECDR VAANCFHQNK NTYNKNYKFL SSSRCRQTSE
QC
