ID   OXLA_BOTMO              Reviewed;         502 AA.
AC   Q6TGQ8; A0A2H4N3D4;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   16-OCT-2019, sequence version 2.
DT   03-MAY-2023, entry version 77.
DE   RecName: Full=L-amino-acid oxidase BmooLAAO-I {ECO:0000303|PubMed:17292326};
DE            Short=LAO;
DE            EC=1.4.3.2 {ECO:0000269|PubMed:17320169};
DE   Flags: Precursor;
OS   Bothrops moojeni (Lance-headed viper) (Caissaca).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX   NCBI_TaxID=98334;
RN   [1] {ECO:0000312|EMBL:ATU85535.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=29107670; DOI=10.1016/j.toxicon.2017.10.025;
RA   Amorim F.G., Morandi-Filho R., Fujimura P.T., Ueira-Vieira C.,
RA   Sampaio S.V.;
RT   "New findings from the first transcriptome of the Bothrops moojeni snake
RT   venom gland.";
RL   Toxicon 140:105-117(2017).
RN   [2] {ECO:0000312|EMBL:AAR31183.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 13-490, FUNCTION, AND 3D-STRUCTURE MODELING.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=17292326; DOI=10.1016/j.bbrc.2006.12.217;
RA   Franca S.C., Kashima S., Roberto P.G., Marins M., Ticli F.K., Pereira J.O.,
RA   Astolfi-Filho S., Stabeli R.G., Magro A.J., Fontes M.R., Sampaio S.V.,
RA   Soares A.M.;
RT   "Molecular approaches for structural characterization of Bothrops L-amino
RT   acid oxidases with antiprotozoal activity: cDNA cloning, comparative
RT   sequence analysis, and molecular modeling.";
RL   Biochem. Biophys. Res. Commun. 355:302-306(2007).
RN   [3]
RP   PROTEIN SEQUENCE OF 19-58, FUNCTION, SUBUNIT, GLYCOSYLATION, CIRCULAR
RP   DICHROISM, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND SUBSTRATE
RP   SPECIFICITY.
RC   TISSUE=Venom;
RX   PubMed=17320169; DOI=10.1016/j.ijbiomac.2007.01.006;
RA   Stabeli R.G., Sant'Ana C.D., Ribeiro P.H., Costa T.R., Ticli F.K.,
RA   Pires M.G., Nomizo A., Albuquerque S., Malta-Neto N.R., Marins M.,
RA   Sampaio S.V., Soares A.M.;
RT   "Cytotoxic L-amino acid oxidase from Bothrops moojeni: biochemical and
RT   functional characterization.";
RL   Int. J. Biol. Macromol. 41:132-140(2007).
RN   [4]
RP   FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=11162565; DOI=10.1006/bbrc.2000.4175;
RA   Tempone A.G., Andrade H.F. Jr., Spencer P.J., Lourenco C.O., Rogero J.R.,
RA   Nascimento N.;
RT   "Bothrops moojeni venom kills Leishmania spp. with hydrogen peroxide
RT   generated by its L-amino acid oxidase.";
RL   Biochem. Biophys. Res. Commun. 280:620-624(2001).
RN   [5]
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).
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 toxicity of the venom
CC       (PubMed:17320169). Shows very high activity on L-Met, and L-Leu, high
CC       activity on L-Ile, L-Phe and L-Tyr and moderate activity on L-His, L-
CC       Val and L-Ala (PubMed:17320169, PubMed:30534149). Exhibits diverse
CC       biological activities, such as edema, apoptosis of tumor cell lines,
CC       antibacterial activities against both Gram-positive and Gram-negative
CC       bacteria, as well as induction of platelet aggregation. Effects of
CC       snake L-amino oxidases on platelets are controversial, since they
CC       either induce aggregation or inhibit agonist-induced aggregation. These
CC       different effects are probably due to different experimental
CC       conditions. Unlike other snake venom L-amino acid oxidases, does not
CC       induce hemorrhage. It may also induce hemolysis. Has parasiticidal
CC       activities against and leishmania, as a result of enzyme-catalyzed
CC       hydrogen peroxide production (PubMed:11162565, PubMed:17292326).
CC       {ECO:0000269|PubMed:11162565, ECO:0000269|PubMed:17292326,
CC       ECO:0000269|PubMed:17320169, ECO:0000269|PubMed:30534149}.
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:17320169,
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:17320169,
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:17320169,
CC         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:0000269|PubMed:17320169};
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:17320169, 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:17320169,
CC         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:17320169,
CC         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:17320169,
CC         ECO:0000269|PubMed:30534149};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-alanine + O2 = H2O2 + NH4(+) + pyruvate;
CC         Xref=Rhea:RHEA:61264, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938,
CC         ChEBI:CHEBI:57972; Evidence={ECO:0000269|PubMed:17320169};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-valine + O2 = 3-methyl-2-oxobutanoate + H2O2 + NH4(+);
CC         Xref=Rhea:RHEA:61252, ChEBI:CHEBI:11851, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938,
CC         ChEBI:CHEBI:57762; Evidence={ECO:0000269|PubMed:17320169};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P81382};
CC   -!- ACTIVITY REGULATION: Its enzymatic activities is reduced when it is
CC       exposed to Ca(2+), Zn(2+), Al(3+), Cu(2+) or Ni(2+) salts.
CC       {ECO:0000269|PubMed:30534149}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.2 mM for L-Phe {ECO:0000269|PubMed:30534149};
CC         KM=0.2 mM for L-Leu {ECO:0000269|PubMed:30534149};
CC         KM=0.3 mM for L-Met {ECO:0000269|PubMed:30534149};
CC         KM=1.1 mM for L-Tyr {ECO:0000269|PubMed:30534149};
CC         KM=1.4 mM for L-Ile {ECO:0000269|PubMed:30534149};
CC         KM=7.4 mM for L-His {ECO:0000269|PubMed:30534149};
CC         KM=6.1 mM for L-Gln {ECO:0000269|PubMed:30534149};
CC       pH dependence:
CC         Optimum pH is 5.5-9.5. {ECO:0000269|PubMed:17320169,
CC         ECO:0000269|PubMed:30534149};
CC       Temperature dependence:
CC         Optimum temperature depends on the study: 5-38 degrees Celsius
CC         (PubMed:17320169) and 60 degrees Celsius (PubMed:30534149).
CC         {ECO:0000269|PubMed:17320169, ECO:0000269|PubMed:30534149};
CC   -!- SUBUNIT: Homodimer; non-covalently linked.
CC       {ECO:0000269|PubMed:11162565, ECO:0000269|PubMed:17320169}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11162565}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:11162565}.
CC   -!- PTM: N-glycosylated (Probable). The enzymatic activity is not affected
CC       by deglycosylation (PubMed:17320169). {ECO:0000269|PubMed:17320169,
CC       ECO:0000305}.
CC   -!- MISCELLANEOUS: Shows low or absent catalytic activity on L-Arg, L-Glu,
CC       L-Asp, L-Lys, L-Asn, L-Ser, L-Thr, L-Pro, L-Gln, L-Gly, and L-Cys
CC       (PubMed:17320169, PubMed:30534149). catalytic activity on L-Val and L-
CC       Ala is moderate or low, depending on the study (PubMed:17320169,
CC       PubMed:30534149). {ECO:0000269|PubMed:17320169,
CC       ECO:0000269|PubMed:30534149}.
CC   -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; MG132016; ATU85535.1; -; mRNA.
DR   EMBL; AY398692; AAR31183.1; -; mRNA.
DR   AlphaFoldDB; Q6TGQ8; -.
DR   SMR; Q6TGQ8; -.
DR   BRENDA; 1.4.3.2; 913.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0001716; F:L-amino-acid oxidase activity; IDA:UniProtKB.
DR   GO; GO:0106329; F:L-phenylalaine oxidase activity; IEA:RHEA.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR   GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR   GO; GO:0044532; P:modulation of apoptotic process in another organism; IDA:UniProtKB.
DR   Gene3D; 3.90.660.10; -; 1.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1.
DR   Gene3D; 1.10.405.10; Guanine Nucleotide Dissociation Inhibitor, domain 1; 1.
DR   InterPro; IPR002937; Amino_oxidase.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR001613; Flavin_amine_oxidase.
DR   PANTHER; PTHR10742:SF235; AMINE OXIDASE; 1.
DR   PANTHER; PTHR10742; FLAVIN MONOAMINE OXIDASE; 1.
DR   Pfam; PF01593; Amino_oxidase; 1.
DR   PRINTS; PR00757; AMINEOXDASEF.
DR   SUPFAM; SSF54373; FAD-linked reductases, C-terminal domain; 1.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
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; Oxidoreductase;
KW   Platelet aggregation activating toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:17320169"
FT   CHAIN           19..502
FT                   /note="L-amino-acid oxidase BmooLAAO-I"
FT                   /evidence="ECO:0000305|PubMed:17320169,
FT                   ECO:0000305|PubMed:29107670"
FT                   /id="PRO_0000273565"
FT   BINDING         61..62
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         81..82
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         89
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         105..108
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         108
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         241
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         279
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         390
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         475
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         482..487
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         482..483
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   CARBOHYD        190
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        28..191
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   DISULFID        349..430
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   CONFLICT        13..17
FT                   /note="AALGS -> RKAPC (in Ref. 2; AAR31183)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        46..47
FT                   /note="ST -> KS (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        490
FT                   /note="S -> W (in Ref. 2; AAR31183)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   502 AA;  56840 MW;  435DFE2429791655 CRC64;
     MNVFFTFSLL FLAALGSCAD DRNPLEECFR ETDYEEFLEI AKNGLSTTSN PKRVVIVGAG
     MSGLSAAYVL ANAGHQVTVL EASERAGGRV KTYRNEKEGW YANLGPMRLP EKHRIVREYI
     RKFDLQLNEF SQENENAWYF IKNIRKRVGE VNKDPGVLEY PVKPSEVGKS AGQLYEESLQ
     KAVEELRRTN CSYMLNKYDT YSTKEYLLKE GNLSPGAVDM IGDLLNEDSG YYVSFIESLK
     HDDIFAYEKR FDEIVGGMDK LPTSMYQAIQ EKVHLNARVI KIQQDVKEVT VTYQTSEKET
     LSVTADYVIV CTTSRAARRI KFEPPLPPKK AHALRSVHYR SGTKIFLTCT KKFWEDDGIH
     GGKSTTDLPS RFIYYPNHNF PNGVGVIIAY GIGDDANYFQ ALDFEDCGDI VINDLSLIHQ
     LPKEEIQAIC RPSMIQRWSL DKYAMGGITT FTPYQFQHFS EALTAPVDRI YFAGEYTAQA
     HGWIDSTIKS GLRAARDVNS AS
//