PA2BA_VIPAA
ID PA2BA_VIPAA Reviewed; 138 AA.
AC P00626;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Basic phospholipase A2 ammodytoxin A;
DE Short=AtxA;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Vipera ammodytes ammodytes (Western 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=8705;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Northern Balkan; TISSUE=Venom gland;
RX PubMed=2048144; DOI=10.1016/0041-0101(91)90112-5;
RA Pungercar J., Kordis D., Strukelj B., Liang N.-S., Gubensek F.;
RT "Cloning and nucleotide sequence of a cDNA encoding ammodytoxin A, the most
RT toxic phospholipase A2 from the venom of long-nosed viper (Vipera
RT ammodytes).";
RL Toxicon 29:269-273(1991).
RN [2]
RP PROTEIN SEQUENCE OF 17-138, AND FUNCTION.
RC STRAIN=Northern Balkan; TISSUE=Venom;
RX PubMed=3986212; DOI=10.1016/0167-4838(85)90312-7;
RA Ritonja A., Gubensek F.;
RT "Ammodytoxin A, a highly lethal phospholipase A2 from Vipera ammodytes
RT ammodytes venom.";
RL Biochim. Biophys. Acta 828:306-312(1985).
RN [3]
RP MUTAGENESIS OF LYS-114; LYS-117 AND LYS-133, AND TOXIC DOSE.
RX PubMed=10377255; DOI=10.1042/bj3410139;
RA Pungercar J., Krizaj I., Liang N.-S., Gubensek F.;
RT "An aromatic, but not a basic, residue is involved in the toxicity of
RT group-II phospholipase A2 neurotoxins.";
RL Biochem. J. 341:139-145(1999).
RN [4]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF 121-TYR-ILE-122 AND
RP 121-TYR--ASN-125.
RX PubMed=11027615; DOI=10.1006/bbrc.2000.3605;
RA Ivanovski G., Copic A., Krizaj I., Gubensek F., Pungercar J.;
RT "The amino acid region 115-119 of ammodytoxins plays an important role in
RT neurotoxicity.";
RL Biochem. Biophys. Res. Commun. 276:1229-1234(2000).
RN [5]
RP MUTAGENESIS OF LYS-114; LYS-117 AND 132-LYS--LYS-137.
RX PubMed=11085916; DOI=10.1042/bj3520251;
RA Prijatelj P., Copic A., Krizaj I., Gubensek F., Pungercar J.;
RT "Charge reversal of ammodytoxin A, a phospholipase A2-toxin, does not
RT abolish its neurotoxicity.";
RL Biochem. J. 352:251-255(2000).
RN [6]
RP FUNCTION.
RX PubMed=11600150; DOI=10.1016/s0041-0101(01)00170-2;
RA Fathi B., Rowan E.G., Harvey A.L.;
RT "The facilitatory actions of snake venom phospholipase A(2) neurotoxins at
RT the neuromuscular junction are not mediated through voltage-gated K(+)
RT channels.";
RL Toxicon 39:1871-1882(2001).
RN [7]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF PHE-39, AND TOXIC DOSE.
RX PubMed=11931665; DOI=10.1042/0264-6021:3630353;
RA Petan T., Krizaj I., Gubensek F., Pungercar J.;
RT "Phenylalanine-24 in the N-terminal region of ammodytoxins is important for
RT both enzymic activity and presynaptic toxicity.";
RL Biochem. J. 363:353-358(2002).
RN [8]
RP AMI2-ATXA CHIMERA.
RX PubMed=12444963; DOI=10.1046/j.1432-1033.2002.03301.x;
RA Prijatelj P., Krizaj I., Kralj B., Gubensek F., Pungercar J.;
RT "The C-terminal region of ammodytoxins is important but not sufficient for
RT neurotoxicity.";
RL Eur. J. Biochem. 269:5759-5764(2002).
RN [9]
RP CALMODULIN-BINDING, AND MUTAGENESIS OF LYS-114; LYS-117; 121-TYR-ILE-122;
RP 121-TYR--ASN-125 AND 132-LYS--LYS-137.
RX PubMed=12846835; DOI=10.1046/j.1432-1033.2003.03679.x;
RA Prijatelj P., Sribar J., Ivanovski G., Krizaj I., Gubensek F.,
RA Pungercar J.;
RT "Identification of a novel binding site for calmodulin in ammodytoxin A, a
RT neurotoxic group IIA phospholipase A2.";
RL Eur. J. Biochem. 270:3018-3025(2003).
RN [10]
RP FUNCTION.
RX PubMed=15485650; DOI=10.1016/j.bbrc.2004.09.144;
RA Petrovic U., Sribar J., Paris A., Rupnik M., Krzan M., Vardjan N.,
RA Gubensek F., Zorec R., Krizaj I.;
RT "Ammodytoxin, a neurotoxic secreted phospholipase A(2), can act in the
RT cytosol of the nerve cell.";
RL Biochem. Biophys. Res. Commun. 324:981-985(2004).
RN [11]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-79; 81-LYS--ARG-84 AND LYS-93, AND
RP TOXIC DOSE.
RX PubMed=15488774; DOI=10.1016/j.bbapap.2004.09.002;
RA Ivanovski G., Petan T., Krizaj I., Gelb M.H., Gubensek F., Pungercar J.;
RT "Basic amino acid residues in the beta-structure region contribute, but not
RT critically, to presynaptic neurotoxicity of ammodytoxin A.";
RL Biochim. Biophys. Acta 1702:217-225(2004).
RN [12]
RP CATALYTIC ACTIVITY, COFACTOR, SITE, AND MUTAGENESIS OF PHE-39; VAL-46 AND
RP 121-TYR--ASN-125.
RC TISSUE=Venom;
RX PubMed=16156665; DOI=10.1021/bi051024r;
RA Petan T., Krizaj I., Gelb M.H., Pungercar J.;
RT "Ammodytoxins, potent presynaptic neurotoxins, are also highly efficient
RT phospholipase A2 enzymes.";
RL Biochemistry 44:12535-12545(2005).
RN [13]
RP FUNCTION, BINDING TO COAGULATION FACTOR X (F10), AND MUTAGENESIS OF ARG-79;
RP 81-LYS--ARG-84; LYS-114; LYS-117; 121-TYR--ASN-125; LYS-132; LYS-133 AND
RP 132-LYS--LYS-137.
RX PubMed=16039772; DOI=10.1016/j.biochi.2005.06.015;
RA Prijatelj P., Charnay M., Ivanovski G., Jenko Z., Pungercar J., Krizaj I.,
RA Faure G.;
RT "The C-terminal and beta-wing regions of ammodytoxin A, a neurotoxic
RT phospholipase A2 from Vipera ammodytes ammodytes, are critical for binding
RT to factor Xa and for anticoagulant effect.";
RL Biochimie 88:69-76(2006).
RN [14]
RP FUNCTION, AND BINDING TO M-TYPE PLA2 RECEPTOR (R-180).
RX PubMed=16815622; DOI=10.1016/j.biochi.2006.06.008;
RA Prijatelj P., Vardjan N., Rowan E.G., Krizaj I., Pungercar J.;
RT "Binding to the high-affinity M-type receptor for secreted phospholipases
RT A(2) is not obligatory for the presynaptic neurotoxicity of ammodytoxin
RT A.";
RL Biochimie 88:1425-1433(2006).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=18261469; DOI=10.1016/j.bbamcr.2008.01.011;
RA Praznikar Z.J., Kovacic L., Rowan E.G., Romih R., Rusmini P., Poletti A.,
RA Krizaj I., Pungercar J.;
RT "A presynaptically toxic secreted phospholipase A2 is internalized into
RT motoneuron-like cells where it is rapidly translocated into the cytosol.";
RL Biochim. Biophys. Acta 1783:1129-1139(2008).
RN [16]
RP REVIEW.
RX PubMed=21726572; DOI=10.1016/j.toxicon.2011.06.009;
RA Krizaj I.;
RT "Ammodytoxin: a window into understanding presynaptic toxicity of secreted
RT phospholipases A(2) and more.";
RL Toxicon 58:219-229(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 17-138, AND DISULFIDE BONDS.
RX PubMed=19857576; DOI=10.1016/j.jsb.2009.10.010;
RA Saul F.A., Prijatelj-Znidarsic P., Vulliez-le Normand B., Villette B.,
RA Raynal B., Pungercar J., Krizaj I., Faure G.;
RT "Comparative structural studies of two natural isoforms of ammodytoxin,
RT phospholipases A2 from Vipera ammodytes ammodytes which differ in
RT neurotoxicity and anticoagulant activity.";
RL J. Struct. Biol. 169:360-369(2010).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that acts as a
CC presynaptic neurotoxin, an inhibitor of blood coagulation, and has been
CC found to bind with high affinity to intracellular proteins. The
CC response of indirectly stimulated neuromuscular preparations to
CC ammodytoxin (Atx) is triphasic. The first phase, the transient
CC inhibition of the acetylcholine (ACh) release, starts soon after the
CC addition of Atx and lasts for several minutes. This phase is probably
CC independent of Atx enzymatic activity. The effect may be due to the
CC specific binding of the toxin to presynaptic receptors. These
CC receptors, called N-type receptors, are still unidentified. It is
CC noteworthy that a neuronal isoform of the M-type PLA2 receptor (R180)
CC has been identified as a high-affinity receptor for Atx in neuronal
CC plasma membranes. It was demonstrated however that this receptor is not
CC essential for expression of neurotoxicity by Atx. The second phase
CC corresponds to an augmentation of neurotransmitter release. A peak is
CC reached 10-20 min after exposure of the preparation to Atx and is
CC followed by a gradual reduction. In this phase, the enzymatic activity
CC of Atx of the mammalian is not significant. It is speculated that the
CC increased release of neurotransmitter in this phase is induced by the
CC interference of Atx with voltage-gated potassium channels. Measurements
CC of ionic currents showed however that voltage-gated potassium channels
CC are not affected by Atx. The third phase of the response of
CC neuromuscular preparations to Atx, which corresponds to a complete and
CC irreversible paralysis, is clearly dependent on the hydrolytic activity
CC of the toxin. In addition to its presynaptic neurotoxicity, Atx shows
CC an anticoagulant activity by binding with high affinity to activated
CC coagulation factor X (F10) thus inhibiting the formation of the
CC prothrombinase complex (FX/FV) and its activity (IC(50) is 20 nM).
CC Surprisingly, Atx was discovered to bind intracellular proteins such as
CC calmodulin (CaM) (IC(50) is 6 nM), 14-3-3 proteins gamma (YWHAG) and
CC epsilon (YWHAE) (by similarity with AtxC), as well as R25 (by
CC similarity with AtxC), a mitochondrial integral membrane protein found
CC in cerebral cortex. These findings raised a doubt about the dogma of
CC the exclusively extracellular action of PLA2s, defended by the
CC potential instability of these molecules in the reducing environment of
CC the eukaryotic cytosol coupled with their possible inability to act as
CC enzymes in this cellular compartment, due to too low concentration of
CC calcium ions. This hypothesis was challenged efficiently by
CC demonstrating the internalization of AtxA into a culture cells, but
CC still remains to be directly demonstrated in vivo. PLA2 catalyzes the
CC calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-
CC phosphoglycerides. {ECO:0000269|PubMed:11600150,
CC ECO:0000269|PubMed:15485650, ECO:0000269|PubMed:16039772,
CC ECO:0000269|PubMed:16815622, ECO:0000269|PubMed:3986212}.
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, ECO:0000269|PubMed:11027615,
CC ECO:0000269|PubMed:11931665, ECO:0000269|PubMed:15488774,
CC ECO:0000269|PubMed:16156665};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:16156665};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000269|PubMed:16156665};
CC -!- SUBUNIT: Monomer. Binds to calmodulin, coagulation factor X (F10), M-
CC type PLA2 receptor (R-180). May also bind to 14-3-3 proteins gamma
CC (YWHAG) and epsilon (YWHAE), and R25, a mitochondrial membrane protein.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18261469}. Host
CC cytoplasm, host cytosol {ECO:0000269|PubMed:18261469}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 0.021 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:10377255, ECO:0000269|PubMed:11931665,
CC ECO:0000269|PubMed:15488774}.
CC -!- MISCELLANEOUS: Does not affect mKv1.1/KCNA1, rKv1.2/KCNA2,
CC mKv1.3/KCNA3, hKv1.5/KCNA5 and mKv3.1/KCNC1 voltage-gated potassium
CC channels. {ECO:0000305|PubMed:11600150}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; X53471; CAA37567.1; -; mRNA.
DR PIR; A39561; PSVIAA.
DR PDB; 3G8G; X-ray; 1.70 A; A=17-138.
DR PDBsum; 3G8G; -.
DR AlphaFoldDB; P00626; -.
DR SMR; P00626; -.
DR EvolutionaryTrace; P00626; -.
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: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; Blood coagulation cascade inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Host cytoplasm; Hydrolase; Lipid degradation; Lipid metabolism;
KW Metal-binding; Neurotoxin; Presynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:3986212"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 ammodytoxin A"
FT /evidence="ECO:0000269|PubMed:3986212"
FT /id="PRO_0000022970"
FT ACT_SITE 63
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT ACT_SITE 105
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 43
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT SITE 18
FT /note="Putative membrane binding site"
FT SITE 19
FT /note="Putative membrane binding site"
FT SITE 34
FT /note="Putative membrane binding site"
FT SITE 35
FT /note="Putative membrane binding site"
FT SITE 39
FT /note="Putative membrane binding site"
FT SITE 46
FT /note="Putative membrane binding site"
FT SITE 76
FT /note="Putative membrane binding site"
FT SITE 77
FT /note="Putative membrane binding site"
FT SITE 79
FT /note="Putative membrane binding site"
FT SITE 82
FT /note="Putative membrane binding site"
FT SITE 124
FT /note="Putative membrane binding site"
FT SITE 125
FT /note="Putative membrane binding site"
FT SITE 129
FT /note="Putative membrane binding site"
FT DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT DISULFID 65..138
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:19857576,
FT ECO:0007744|PDB:3G8G"
FT MUTAGEN 39
FT /note="F->A: Is 4-fold less toxic than wild-type AtxA, is
FT similarly enzymatically active on anionic POPG vesicles and
FT 3.2-fold less active on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:11931665,
FT ECO:0000269|PubMed:16156665"
FT MUTAGEN 39
FT /note="F->N: Is 130-fold less toxic than wild-type AtxA, is
FT similarly enzymatically active on anionic POPG vesicles and
FT 3.5-fold less active on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:11931665,
FT ECO:0000269|PubMed:16156665"
FT MUTAGEN 39
FT /note="F->S: Is 18-fold less toxic than wild-type AtxA, is
FT similarly enzymatically active on anionic POPG vesicles and
FT 5.4-fold less active on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:11931665,
FT ECO:0000269|PubMed:16156665"
FT MUTAGEN 39
FT /note="F->W: Is 8-fold less toxic than wild-type AtxA, is
FT similarly enzymatically active on anionic POPG vesicles and
FT on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:11931665,
FT ECO:0000269|PubMed:16156665"
FT MUTAGEN 39
FT /note="F->Y: Is 16-fold less toxic than wild-type AtxA, is
FT similarly enzymatically active on anionic POPG vesicles and
FT on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:11931665,
FT ECO:0000269|PubMed:16156665"
FT MUTAGEN 46
FT /note="V->W: Is 6-fold less toxic than wild-type AtxA, has
FT 2-fold higher enzymatic activity on anionic POPG vesicles
FT and 27-fold more active on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:16156665"
FT MUTAGEN 79
FT /note="R->E: Is 4-fold less toxic than wild-type AtxA, has
FT 2.5-fold lower enzymatic activity on anionic POPG vesicles
FT and 6-fold on zwitterionic POPC vesicles, and has 8.5-fold
FT lower activity in inhibiting prothrombinase activity."
FT /evidence="ECO:0000269|PubMed:15488774,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 79
FT /note="R->I: Is 1.5-fold less toxic than wild-type AtxA,
FT and has 1.5-fold higher enzymatic activity on anionic POPG
FT and 3.5-fold on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:15488774,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 79
FT /note="R->K: Is 2.4-fold less toxic than wild-type AtxA,
FT and has 1.6-fold lower enzymatic activity on anionic POPG
FT vesicles and 1.6-fold on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:15488774,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 79
FT /note="R->S: Is 2.6-fold less toxic than wild-type AtxA,
FT has 1.4-fold lower enzymatic activity on anionic POPG
FT vesicles and 1.2-fold on zwitterionic POPC vesicles, and
FT has 3.5-fold lower activity in inhibiting prothrombinase
FT activity."
FT /evidence="ECO:0000269|PubMed:15488774,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 81..84
FT /note="KYHR->SYSL: Is 13-fold less toxic than wild-type
FT AtxA, has 1.2-fold lower enzymatic activity on anionic POPG
FT vesicles and 1.7-fold on zwitterionic POPC vesicles, and
FT has 19-fold lower activity in inhibiting prothrombinase
FT activity."
FT /evidence="ECO:0000269|PubMed:15488774,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 93
FT /note="K->A: Is 1.1-fold less toxic than wild-type AtxA,
FT and has 1.3-fold lower enzymatic activity on anionic POPG
FT vesicles and 1.4-fold on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:15488774"
FT MUTAGEN 93
FT /note="K->E: Is 1.5-fold less toxic than wild-type AtxA,
FT and has 1.1-fold lower enzymatic activity on anionic POPG
FT vesicles and 1.2-fold on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:15488774"
FT MUTAGEN 93
FT /note="K->G: Is 1.6-fold less toxic than wild-type AtxA,
FT and has 1.1-fold lower enzymatic activity on anionic POPG
FT vesicles and 1.7-fold on zwitterionic POPC vesicles."
FT /evidence="ECO:0000269|PubMed:15488774"
FT MUTAGEN 93
FT /note="K->R: Is 1.5-fold less toxic than wild-type AtxA,
FT and is similarly enzymatically active on anionic POPG
FT vesicles and 1.4-fold less active on zwitterionic POPC
FT vesicles."
FT /evidence="ECO:0000269|PubMed:15488774"
FT MUTAGEN 114
FT /note="K->N: Is 3-fold less toxic (by intraperitoneal
FT injection) than wild-type AtxA (by intravenous injection),
FT has 1.6-fold higher enzymatic activity, has 2.8-fold lower
FT binding affinity for CaM, and has similar binding affinity
FT for bovine brain receptor; when associated with N-117."
FT /evidence="ECO:0000269|PubMed:10377255,
FT ECO:0000269|PubMed:11085916, ECO:0000269|PubMed:12846835,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 114
FT /note="K->N: Is 30-fold less toxic than wild-type AtxA, has
FT 3-fold higher enzymatic activity, has 20-fold lower
FT activity in inhibiting prothrombinase activity, and has
FT 4.5-fold lower binding affinity to CaM; when associated
FT with N-117 and 132-T--E-137."
FT /evidence="ECO:0000269|PubMed:10377255,
FT ECO:0000269|PubMed:11085916, ECO:0000269|PubMed:12846835,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 117
FT /note="K->N: Is 3-fold less toxic (by intraperitoneal
FT injection) than wild-type AtxA (by intravenous injection),
FT has 1.6-fold higher enzymatic activity, has 2.8-fold lower
FT binding affinity for CaM, and has similar binding affinity
FT for bovine brain receptor; when associated with N-114."
FT /evidence="ECO:0000269|PubMed:10377255,
FT ECO:0000269|PubMed:11085916, ECO:0000269|PubMed:12846835,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 117
FT /note="K->N: Is 30-fold less toxic than wild-type AtxA, has
FT 3-fold higher enzymatic activity, has 20-fold lower
FT activity in inhibiting prothrombinase activity, and has
FT 4.5-fold lower binding affinity to CaM; when associated
FT with N-114 and 132-T--E-137."
FT /evidence="ECO:0000269|PubMed:10377255,
FT ECO:0000269|PubMed:11085916, ECO:0000269|PubMed:12846835,
FT ECO:0000269|PubMed:16039772"
FT MUTAGEN 121..125
FT /note="YIYRN->KKYML: Is >200-fold less toxic than wild-type
FT AtxA, is similarly enzymatically active on anionic POPG
FT vesicles, and 5-fold more active on zwitterionic POPC
FT vesicles, has 3.5-fold lower activity in inhibiting
FT prothrombinase activity, and has 8.3-fold lower binding
FT affinity for CaM."
FT /evidence="ECO:0000269|PubMed:11027615,
FT ECO:0000269|PubMed:12846835, ECO:0000269|PubMed:16039772,
FT ECO:0000269|PubMed:16156665"
FT MUTAGEN 121..122
FT /note="YI->KK: Is <200-fold less toxic than wild-type AtxA,
FT has 2-fold lower enzymatic activity (on phosphatidylcholine
FT micelle), and has 3.5-fold lower binding affinity for CaM."
FT /evidence="ECO:0000269|PubMed:11027615,
FT ECO:0000269|PubMed:12846835"
FT MUTAGEN 132..137
FT /note="KKESEK->TETSEE: Is 30-fold less toxic than wild-type
FT AtxA, has 3-fold higher enzymatic activity, has 20-fold
FT lower activity in inhibiting prothrombinase activity, and
FT has 4.5-fold lower binding affinity for CaM; when
FT associated with N-114 and N-117."
FT /evidence="ECO:0000269|PubMed:11085916,
FT ECO:0000269|PubMed:12846835, ECO:0000269|PubMed:16039772"
FT MUTAGEN 132
FT /note="K->T: Is 2-fold less toxic than wild-type AtxA, has
FT slight lower enzymatic activity, has 7-fold lower activity
FT in inhibiting prothrombinase activity and has 3.3-fold
FT lower binding affinity to CaM."
FT /evidence="ECO:0000269|PubMed:16039772"
FT MUTAGEN 133
FT /note="K->E: Is 2-fold less toxic (by intraperitoneal
FT injection) than wild-type AtxA (by intravenous injection),
FT has similar enzymatic activity, has a slightly weaker
FT binding affinity for bovine brain receptor, has 13-fold
FT lower activity in inhibiting prothrombinase activity, and
FT has 2.3-fold lower binding affinity for CaM."
FT /evidence="ECO:0000269|PubMed:10377255,
FT ECO:0000269|PubMed:16039772"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:3G8G"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:3G8G"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:3G8G"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:3G8G"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:3G8G"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:3G8G"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:3G8G"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:3G8G"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:3G8G"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:3G8G"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:3G8G"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3G8G"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:3G8G"
SQ SEQUENCE 138 AA; 15531 MW; D9FAF40A04E31BB2 CRC64;
MRTLWIVAVC LIGVEGSLLE FGMMILGETG KNPLTSYSFY GCYCGVGGKG TPKDATDRCC
FVHDCCYGNL PDCSPKTDRY KYHRENGAIV CGKGTSCENR ICECDRAAAI CFRKNLKTYN
YIYRNYPDFL CKKESEKC
