OXLA2_BOTJR
ID OXLA2_BOTJR Reviewed; 116 AA.
AC P0DV78;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 1.
DT 03-AUG-2022, entry version 2.
DE RecName: Full=L-amino-acid oxidase BjussuLAAO-II {ECO:0000303|PubMed:28495622};
DE Short=LAO;
DE EC=1.4.3.2 {ECO:0000269|PubMed:28495622};
DE Flags: Fragments;
OS Bothrops jararacussu (Jararacussu).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8726;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RC TISSUE=Venom;
RX PubMed=28495622; DOI=10.1016/j.ijbiomac.2017.05.025;
RA Carone S.E.I., Costa T.R., Burin S.M., Cintra A.C.O., Zoccal K.F.,
RA Bianchini F.J., Tucci L.F.F., Franco J.J., Torqueti M.R., Faccioli L.H.,
RA Albuquerque S., Castro F.A., Sampaio S.V.;
RT "A new l-amino acid oxidase from Bothrops jararacussu snake venom:
RT isolation, partial characterization, and assessment of pro-apoptotic and
RT antiprotozoal activities.";
RL Int. J. Biol. Macromol. 103:25-35(2017).
RN [2]
RP FUNCTION.
RX PubMed=29222016; DOI=10.1016/j.ijbiomac.2017.12.015;
RA Machado A.R.T., Aissa A.F., Ribeiro D.L., Hernandes L.C., Machado C.S.,
RA Bianchi M.L.P., Sampaio S.V., Antunes L.M.G.;
RT "The toxin BjussuLAAO-II induces oxidative stress and DNA damage,
RT upregulates the inflammatory cytokine genes TNF and IL6, and downregulates
RT the apoptotic-related genes BAX, BCL2 and RELA in human Caco-2 cells.";
RL Int. J. Biol. Macromol. 109:212-219(2018).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=30534149; DOI=10.1186/s40409-018-0172-9;
RA Costa T.R., Carone S.E.I., Tucci L.F.F., Menaldo D.L., Rosa-Garzon N.G.,
RA Cabral H., Sampaio S.V.;
RT "Kinetic investigations and stability studies of two Bothrops L-amino acid
RT oxidases.";
RL J. Venom. Anim. Toxins Incl. Trop. Dis. 24:37-37(2018).
RN [4]
RP FUNCTION.
RX PubMed=30654040; DOI=10.1016/j.ijbiomac.2019.01.059;
RA Machado A.R.T., Aissa A.F., Ribeiro D.L., Costa T.R., Ferreira R.S. Jr.,
RA Sampaio S.V., Antunes L.M.G.;
RT "Cytotoxic, genotoxic, and oxidative stress-inducing effect of an l-amino
RT acid oxidase isolated from Bothrops jararacussu venom in a co-culture model
RT of HepG2 and HUVEC cells.";
RL Int. J. Biol. Macromol. 127:425-432(2019).
CC -!- FUNCTION: Catalyzes an oxidative deamination of predominantly
CC hydrophobic and aromatic L-amino acids, thus producing hydrogen
CC peroxide that may contribute to the diverse toxic effects of this
CC enzyme (PubMed:28495622) (By similarity). Shows very high enzymatic
CC activity on L-Met and L-Leu, high activity on L-Ile, L-Phe and L-Tyr
CC and moderate activity on L-His (PubMed:28495622, PubMed:30534149).
CC Exhibits diverse biological activities, such as hemorrhage, hemolysis,
CC edema, apoptosis of vascular endothelial cells or tumor cell lines, and
CC antibacterial, as well as regulation of platelet aggregation (By
CC similarity). Effects of snake L-amino oxidases on platelets are
CC controversial, since they either induce aggregation or inhibit agonist-
CC induced aggregation (By similarity). These different effects are
CC probably due to different experimental conditions (By similarity). In
CC vitro, has a strong antiprotozoal effect against Leishmania amazonensis
CC (IC(50)=4.56 ug/mL) and Trypanosoma cruzi (IC(50)=4.85 ug/mL)
CC (PubMed:28495622). It also causes cell death and DNA damage in
CC hepatocarcinoma cells (HepG2) in vitro by inducing oxidative stress
CC (PubMed:30654040). It exerts cytotoxicity towards colorectal
CC adenocarcinomahuman cells (Caco-2) by acting on multiple intracellular
CC targets (PubMed:29222016). It diminishes cell viability by decreasing
CC mitochondrial activity, the activity of acid phosphatases, and
CC lysosomal function (PubMed:29222016). In addition, it increases
CC intracellular levels of reactive oxygen species and DNA damage, it
CC elevates the expression of the pro-inflammatory cytokine genes TNF and
CC IL6, and lowers the expression of the apoptotic-related genes
CC (PubMed:29222016). Also induces cytotoxicity (IC(50)=1.80 ug/mL) and
CC apoptosis in MCF7 cells (a human breast adeno-carcinoma cell line) by
CC activating the intrinsic and extrinsic apoptosis pathways, but are not
CC cytotoxic towards MCF10A cells (a non-tumorigenic human breast
CC epithelial cell line) (PubMed:28495622). {ECO:0000250|UniProtKB:Q6TGQ9,
CC ECO:0000269|PubMed:28495622, ECO:0000269|PubMed:29222016,
CC ECO:0000269|PubMed:30534149, ECO:0000269|PubMed:30654040}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an L-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 +
CC NH4(+); Xref=Rhea:RHEA:13781, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35179,
CC ChEBI:CHEBI:59869; EC=1.4.3.2; Evidence={ECO:0000269|PubMed:28495622,
CC ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-leucine + O2 = 4-methyl-2-oxopentanoate + H2O2 +
CC NH4(+); Xref=Rhea:RHEA:60996, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17865, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57427; Evidence={ECO:0000269|PubMed:28495622,
CC ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-phenylalanine + O2 = 3-phenylpyruvate + H2O2 + NH4(+);
CC Xref=Rhea:RHEA:61240, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:58095; Evidence={ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-methionine + O2 = 4-methylsulfanyl-2-oxobutanoate +
CC H2O2 + NH4(+); Xref=Rhea:RHEA:61236, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16723,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:57844;
CC Evidence={ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-isoleucine + O2 = (S)-3-methyl-2-oxopentanoate + H2O2
CC + NH4(+); Xref=Rhea:RHEA:61232, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35146,
CC ChEBI:CHEBI:58045; Evidence={ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-histidine + O2 = 3-(imidazol-5-yl)pyruvate + H2O2 +
CC NH4(+); Xref=Rhea:RHEA:61228, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:57595,
CC ChEBI:CHEBI:58133; Evidence={ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-tyrosine + O2 = 3-(4-hydroxyphenyl)pyruvate + H2O2 +
CC NH4(+); Xref=Rhea:RHEA:61248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:36242,
CC ChEBI:CHEBI:58315; Evidence={ECO:0000269|PubMed:30534149};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-tryptophan + O2 = H2O2 + indole-3-pyruvate + NH4(+);
CC Xref=Rhea:RHEA:61244, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17640, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57912; Evidence={ECO:0000250|UniProtKB:Q6TGQ9};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q6TGQ9};
CC -!- ACTIVITY REGULATION: Its enzymatic activities is reduced by the
CC presence of Zn(2+), Al(3+), Cu(2+), Na(+) or Ni(2+) salts.
CC {ECO:0000269|PubMed:30534149}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 mM for L-Phe {ECO:0000269|PubMed:30534149};
CC KM=0.3 mM for L-Leu {ECO:0000269|PubMed:30534149};
CC KM=0.6 mM for L-Met {ECO:0000269|PubMed:30534149};
CC KM=1.1 mM for L-Tyr {ECO:0000269|PubMed:30534149};
CC KM=2.0 mM for L-Ile {ECO:0000269|PubMed:30534149};
CC KM=14.1 mM for L-His {ECO:0000269|PubMed:30534149};
CC KM=3.2 mM for L-Gln {ECO:0000269|PubMed:30534149};
CC pH dependence:
CC Optimum pH is 6-9. {ECO:0000269|PubMed:30534149};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius.
CC {ECO:0000269|PubMed:30534149};
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:Q6TGQ9}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28495622}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28495622}.
CC -!- PTM: Glycosylated. {ECO:0000255}.
CC -!- MISCELLANEOUS: Shows low or absent catalytic activity on L-Arg, L-Glu,
CC L-Val, L-Ala, L-Asp, L-Lys, L-Asn, L-Ser, L-Thr, L-Pro, L-Gln, L-Gly,
CC and L-Cys. {ECO:0000269|PubMed:30534149}.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC subfamily. {ECO:0000305}.
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DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Apoptosis; Cytolysis; Direct protein sequencing;
KW Disulfide bond; FAD; Flavoprotein; Glycoprotein; Hemolysis;
KW Hemostasis impairing toxin; Nucleotide-binding; Oxidoreductase; Secreted;
KW Toxin.
FT CHAIN 1..>116
FT /note="L-amino-acid oxidase BjussuLAAO-II"
FT /evidence="ECO:0000305|PubMed:28495622"
FT /id="PRO_0000455521"
FT BINDING 42..45
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6TGQ9"
FT BINDING 45
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT BINDING 78
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT DISULFID 10..?
FT /evidence="ECO:0000305"
FT NON_CONS 34..35
FT /evidence="ECO:0000305|PubMed:28495622"
FT NON_CONS 45..46
FT /evidence="ECO:0000305|PubMed:28495622"
FT NON_CONS 61..62
FT /evidence="ECO:0000305|PubMed:28495622"
FT NON_CONS 76..77
FT /evidence="ECO:0000305|PubMed:28495622"
FT NON_CONS 96..97
FT /evidence="ECO:0000305|PubMed:28495622"
FT NON_CONS 108..109
FT /evidence="ECO:0000305|PubMed:28495622"
FT NON_TER 116
FT /evidence="ECO:0000305|PubMed:28495622"
SQ SEQUENCE 116 AA; 13515 MW; AF91C6CAD018F9A3 CRC64;
ADDRNPLEEC FRETDYEEFL EIARNGLSDT DNPKEGWYAN LGPMRLNEFS QENENAWYFI
KDPGVLDYPV KPSEVGKHDD IFAYEKRFDE IVGGMDKEVT VTYQTSEKFE PPLPPK
