ID   OXLA_DABRR              Reviewed;         504 AA.
AC   G8XQX1;
DT   11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2012, sequence version 1.
DT   03-MAY-2023, entry version 43.
DE   RecName: Full=L-amino-acid oxidase;
DE            Short=DrLAO {ECO:0000303|PubMed:21802487};
DE            Short=LAAO;
DE            EC=1.4.3.2 {ECO:0000269|PubMed:21802487};
DE   Flags: Precursor;
OS   Daboia russelii (Russel's viper) (Vipera russelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Viperinae; Daboia.
OX   NCBI_TaxID=8707;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-38, FUNCTION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-241, MASS SPECTROMETRY,
RP   SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, 3D-STRUCTURE
RP   MODELING IN COMPLEX WITH SUBSTRATE, AND SUBSTRATE SPECIFICITY.
RC   STRAIN=Eastern India; TISSUE=Venom, and Venom gland;
RX   PubMed=21802487; DOI=10.1016/j.biochi.2011.07.022;
RA   Chen H.-S., Wang Y.-M., Huang W.-T., Huang K.-F., Tsai I.-H.;
RT   "Cloning, characterization and mutagenesis of Russell's viper venom L-amino
RT   acid oxidase: insights into its catalytic mechanism.";
RL   Biochimie 94:335-344(2012).
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:21802487). Is highly active on L-Tyr followed by L-Phe,
CC       L-Met, L-Leu, L-Trp, and weakly active on L-Ile, L-Arg, L-Val, L-Lys,
CC       and L-Ala (PubMed:21802487). Inhibits ADP- and collagen-induced
CC       platelet aggregation (PubMed:21802487). This inhibition is inhibited by
CC       catalase, indicating the importance of generated H(2)O(2) for the
CC       inhibitory effect (PubMed:21802487). This effect on platelets among
CC       snake L-amino-acid oxidases is however controversial, since some of
CC       them induce aggregation, whereas the other inhibit agonist-induced
CC       aggregation (By similarity). In vivo, this enzyme induces a rapid,
CC       substantial and reversible increase in the paw volume of mice (edema)
CC       (PubMed:21802487). In addition, myofibrosis, and inflammatory cell
CC       infiltration on the paw tissue are also observed (PubMed:21802487).
CC       {ECO:0000250|UniProtKB:P0CC17, ECO:0000269|PubMed:21802487}.
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;
CC         Evidence={ECO:0000269|PubMed:21802487};
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:21802487};
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:21802487};
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:21802487};
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:21802487};
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:21802487};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P81382};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.081 mM for L-Tyr (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=0.142 mM for L-Phe (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=0.373 mM for L-Met (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=0.318 mM for L-Trp (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=0.49 mM for L-Leu (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=1.4 mM for L-Ile (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=12.2 mM for L-Arg (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=13.92 mM for L-Val (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=64 mM for L-Lys (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC         KM=116.48 mM for L-Ala (at pH 7.5 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:21802487};
CC   -!- SUBUNIT: Homodimer; non-covalently linked.
CC       {ECO:0000250|UniProtKB:P81382}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21802487}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:21802487}.
CC   -!- MASS SPECTROMETRY: Mass=62025; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:21802487};
CC   -!- MISCELLANEOUS: Negative results: does not induce dermal hemorrhage when
CC       subcutaneously injected into mice at the dose of 40 ug.
CC       {ECO:0000305|PubMed:21802487}.
CC   -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC       subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; EU663622; ACF70483.1; -; mRNA.
DR   AlphaFoldDB; G8XQX1; -.
DR   SMR; G8XQX1; -.
DR   SABIO-RK; G8XQX1; -.
DR   GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR   GO; GO:0043655; C:host extracellular space; NAS:UniProtKB.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; TAS: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:0044398; P:envenomation resulting in induction of edema in another organism; IDA:UniProtKB.
DR   GO; GO:0044477; P:envenomation resulting in negative regulation of platelet aggregation in another organism; IDA:UniProtKB.
DR   GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
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   PANTHER; PTHR10742:SF235; 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   Cytolysis; Direct protein sequencing; Disulfide bond; FAD; Flavoprotein;
KW   Glycoprotein; Hemolysis; Hemostasis impairing toxin; Oxidoreductase;
KW   Platelet aggregation inhibiting toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:21802487"
FT   CHAIN           19..504
FT                   /note="L-amino-acid oxidase"
FT                   /id="PRO_5000825648"
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   CARBOHYD        379
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   MUTAGEN         241
FT                   /note="H->A: Shows high reactivity toward L-Arg, but does
FT                   not induce change toward L-Leu, L-Phe and L-Met."
FT                   /evidence="ECO:0000269|PubMed:21802487"
FT   MUTAGEN         241
FT                   /note="H->N: No change in activity."
FT                   /evidence="ECO:0000269|PubMed:21802487"
FT   MUTAGEN         241
FT                   /note="H->S: Shows middle reactivity toward L-Arg and
FT                   L-Phe, but does not induce change toward L-Leu, and L-Met."
FT                   /evidence="ECO:0000269|PubMed:21802487"
SQ   SEQUENCE   504 AA;  56888 MW;  938FBF23BBAA7681 CRC64;
     MNVFFMFSLL FLATLGSCAD DKNPLEECFR EDDYEEFLEI AKNGLKKTSN PKHIVIVGAG
     MSGLSAAYVL AGAGHKVTVL EASERPGGRV RTHRNVKEGW YANLGPMRVP EKHRIIREYI
     RKFGLKLNEF VQETENGWYF IKNIRKRVGE VKKDPGLLKY PVKPSEAGKS AGQLYQESLG
     KAVEELKRTN CSYILNKYDT YSTKEYLIKE GNLSPGAVDM IGDLLNEDSG YYVSFIESLK
     HDDIFAYEKR FDEIVGGMDQ LPTSMYRAIE ESVHFKARVI KIQQNAEKVT VTYQTTQKNL
     LLETADYVIV CTTSRAARRI TFKPPLPPKK AHALRSVHYR SGTKIFLTCT KKFWEDDGIQ
     GGKSTTDLPS RFIYYPNHNF TTGVGVIIAY GIGDDANFFQ ALNLNECADI VFNDLSSIHQ
     LPKKDLQTFC YPSIIQKWSL DKYAMGAITT FTPYQFQHFS EALTAPVGRI FFAGEYTANA
     HGWIDSTIKS GLTAARDVNR ASEL
//