ID   OXLA_CRODU              Reviewed;         516 AA.
AC   C0HJE7; P0C2D2;
DT   30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   31-JUL-2019, sequence version 2.
DT   02-SEP-2026, entry version 26.
DE   RecName: Full=L-amino acid oxidase bordonein-L {ECO:0000303|PubMed:26273287};
DE            Short=Casca LAO {ECO:0000303|PubMed:16307769};
DE            Short=LAAO {ECO:0000303|PubMed:26273287};
DE            Short=LAO {ECO:0000250|UniProtKB:P0C2D2};
DE            EC=1.4.3.2 {ECO:0000269|PubMed:16307769, ECO:0000269|PubMed:26273287, ECO:0000269|PubMed:31078582};
DE   Flags: Precursor;
OS   Crotalus durissus terrificus (South American rattlesnake).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX   NCBI_TaxID=8732;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=30270628; DOI=10.1021/acs.jproteome.8b00610;
RA   Wiezel G.A., Shibao P.Y.T., Cologna C.T., Morandi Filho R.,
RA   Ueira-Vieira C., De Pauw E., Quinton L., Arantes E.C.;
RT   "In-depth venome of the Brazilian rattlesnake crotalus durissus terrificus:
RT   an integrative approach combining its venom gland transcriptome and venom
RT   proteome.";
RL   J. Proteome Res. 17:3941-3958(2018).
RN   [2]
RP   PROTEIN SEQUENCE OF 19-79, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=16307769; DOI=10.1016/j.toxicon.2005.09.008;
RA   Toyama M.H., Toyama Dde O., Passero L.F., Laurenti M.D., Corbett C.E.,
RA   Tomokane T.Y., Fonseca F.V., Antunes E., Joazeiro P.P., Beriam L.O.,
RA   Martins M.A., Monteiro H.S., Fonteles M.C.;
RT   "Isolation of a new L-amino acid oxidase from Crotalus durissus cascavella
RT   venom.";
RL   Toxicon 47:47-57(2006).
RN   [3]
RP   PROTEIN SEQUENCE OF 19-57, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=26273287; DOI=10.1186/s40409-015-0025-8;
RA   Bordon K.C., Wiezel G.A., Cabral H., Arantes E.C.;
RT   "Bordonein-L, a new L-amino acid oxidase from Crotalus durissus terrificus
RT   snake venom: isolation, preliminary characterization and enzyme
RT   stability.";
RL   J. Venom. Anim. Toxins Incl. Trop. Dis. 21:26-26(2015).
RN   [4]
RP   PROTEIN SEQUENCE OF 19-31 AND 184-203, IDENTIFICATION BY MASS SPECTROMETRY,
RP   3D-STRUCTURE MODELING, GLYCOSYLATION AT ASN-379, DISULFIDE BOND,
RP   BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE
RP   SPECIFICITY.
RC   TISSUE=Venom;
RX   PubMed=31078582; DOI=10.1016/j.biochi.2019.05.009;
RA   Wiezel G.A., Rustiguel J.K., Morgenstern D., Zoccal K.F., Faccioli L.H.,
RA   Nonato M.C., Ueberheide B., Arantes E.C.;
RT   "Insights into the structure, function and stability of bordonein-L, the
RT   first L-amino acid oxidase from Crotalus durissus terrificus snake venom.";
RL   Biochimie 163:33-49(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:16307769, PubMed:26273287, PubMed:31078582). Is highly
CC       active on L-Met, L-Leu, L-Trp, and L-Phe, moderately active on L-Ile,
CC       L-His, and L-Arg, and weakly or not active on L-Gln, L-Val, L-Asn, L-
CC       Ala, L-Lys, L-Ser, L-Thr, L-Pro, L-Asp, L-Gly, L-Tyr, L-Cys and L-Glu
CC       (PubMed:16307769, PubMed:31078582). This enzyme exhibits diverse
CC       biological activities, such as hemorrhage, hemolysis, edema, apoptosis
CC       of vascular endothelial cells or tumor cell lines, antibacterial and
CC       antiparasitic activities, as well as regulation of platelet aggregation
CC       (PubMed:16307769, PubMed:26273287). Its effect on platelets is
CC       controversial, since it either induces aggregation or inhibits agonist-
CC       induced aggregation (PubMed:26273287). These different effects are
CC       probably due to different experimental conditions (PubMed:26273287). In
CC       vitro, the enzyme exhibits cytotoxicity against fibroblast cell line
CC       and kills Leishmania amazonensis promastigotes, intensified by
CC       substrate addition (PubMed:31078582). {ECO:0000269|PubMed:26273287,
CC       ECO:0000269|PubMed:31078582}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an L-alpha-amino acid + O2 + H2O = 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:26273287,
CC         ECO:0000269|PubMed:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-leucine + O2 + H2O = 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:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-phenylalanine + O2 + H2O = 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:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tryptophan + O2 + H2O = indole-3-pyruvate + H2O2 + 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:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-methionine + O2 + H2O = 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:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-isoleucine + O2 + H2O = (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:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-arginine + O2 + H2O = 5-guanidino-2-oxopentanoate + H2O2 +
CC         NH4(+); Xref=Rhea:RHEA:51404, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32682,
CC         ChEBI:CHEBI:58489; Evidence={ECO:0000269|PubMed:31078582};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-histidine + O2 + H2O = 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:31078582};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000269|PubMed:16307769};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.14 mM for L-Phe {ECO:0000269|PubMed:31078582};
CC         KM=0.48 mM for L-Trp {ECO:0000269|PubMed:31078582};
CC         KM=0.97 mM for L-Met {ECO:0000269|PubMed:31078582};
CC         KM=3.9 mM for L-Ile {ECO:0000269|PubMed:31078582};
CC         KM=0.58 mM for L-Leu {ECO:0000269|PubMed:31078582};
CC         KM=46.7 uM for L-Leu {ECO:0000269|PubMed:16307769};
CC       pH dependence:
CC         Optimum pH is 6.5-7.0 (PubMed:16307769, PubMed:26273287). Activity is
CC         reduced to about 70% and 60% after incubation at pH 5.0 and pH 9.0,
CC         respectively, for 1 hour (PubMed:26273287).
CC         {ECO:0000269|PubMed:16307769, ECO:0000269|PubMed:26273287};
CC   -!- SUBUNIT: Homodimer; non-covalently linked.
CC       {ECO:0000269|PubMed:16307769, ECO:0000269|PubMed:26273287}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16307769,
CC       ECO:0000269|PubMed:26273287}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:16307769, ECO:0000305|PubMed:26273287}.
CC   -!- PTM: N-glycosylated (PubMed:26273287, PubMed:31078582). N-glycan
CC       probably consists of the disaccharide N-acetylglucosamine-fucose
CC       (HexNAc-Fuc) (PubMed:31078582). {ECO:0000269|PubMed:26273287,
CC       ECO:0000269|PubMed:31078582}.
CC   -!- MASS SPECTROMETRY: Mass=58702; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:26273287};
CC   -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC       subfamily. {ECO:0000305}.
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DR   AlphaFoldDB; C0HJE7; -.
DR   SMR; C0HJE7; -.
DR   iPTMnet; C0HJE7; -.
DR   BRENDA; 1.4.3.2; 1711.
DR   GO; GO:0005576; C:extracellular region; EXP:UniProtKB.
DR   GO; GO:0001716; F:L-amino-acid oxidase activity; EXP:UniProtKB.
DR   GO; GO:0106329; F:L-phenylalaine oxidase activity; EXP:UniProtKB.
DR   GO; GO:0009063; P:amino acid catabolic process; IEA:TreeGrafter.
DR   FunFam; 1.10.405.10:FF:000004; Amine oxidase; 1.
DR   FunFam; 3.50.50.60:FF:000450; Amine oxidase; 1.
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; IPR050281; Flavin_monoamine_oxidase.
DR   PANTHER; PTHR10742:SF355; AMINE OXIDASE; 1.
DR   PANTHER; PTHR10742; FLAVIN MONOAMINE OXIDASE; 1.
DR   Pfam; PF01593; Amino_oxidase; 1.
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;
KW   Hemostasis impairing toxin; Oxidoreductase;
KW   Platelet aggregation inhibiting toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..516
FT                   /note="L-amino acid oxidase bordonein-L"
FT                   /evidence="ECO:0000305|PubMed:16307769,
FT                   ECO:0000305|PubMed:26273287, ECO:0000305|PubMed:31078582"
FT                   /id="PRO_0000438321"
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         103..106
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         106
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P81382"
FT   BINDING         239
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        379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305|PubMed:31078582"
FT   DISULFID        28..189
FT                   /evidence="ECO:0000269|PubMed:31078582"
FT   DISULFID        349..430
FT                   /evidence="ECO:0000269|PubMed:31078582"
FT   CONFLICT        27
FT                   /note="E -> Q (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        44..47
FT                   /note="GLTV -> NLKA (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        71..73
FT                   /note="AGA -> SGG (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   516 AA;  58919 MW;  95B518BF40095212 CRC64;
     MNVFFMFSLL FLAALGSCAH DRNPLEECFR ETDYEEFLEI ARNGLTVTSN PKHVVIVGAG
     MAGLSAAYVL AGAGHQVTVL EASERVGGRV RTYRKKDWYA NLGPMRLPTK HRIVREYIRK
     FGLQLNEFFQ ENENAWYFIK NIRKRVREVK NNPGILEYPV KPSEEGKSAA QLYVESLRKV
     VKELKRTNCK YILDKYDTYS TKEYLLKEGN LSPGAVDMIG DLLNEDSGYY VSFIESLKHD
     DIFGYEKRFD EIVGGMDQLP TSMYEAIKEK VQVHFNARVI EIQQNDRETK VTYQTSANEM
     SSVTADYVIV CTTSRAARRI KFEPPLPPKK AHALRSVHYR SGTKIFLTCK RKFWEDDGIR
     GGKSTTDLPS RFIYYPNHNF TSGVGVIIAY GIGDDANFFQ ALDFKDCADI VINDLSLIHQ
     LPKEDIQTFC RPSMIQRWSL DKYAMGGITT FTPYQFQHFS EALTAPFKRI YFAGEYTAQF
     HGWIDSTIKS GLTAARDVNR ASENPSGIHL SNDNEF
//