OXLA_LACMT
ID OXLA_LACMT Reviewed; 516 AA.
AC J7H670;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=L-amino acid oxidase Lm29 {ECO:0000303|PubMed:18541473};
DE AltName: Full=LmLAAO {ECO:0000303|PubMed:22963728};
DE Short=LAO;
DE EC=1.4.3.2 {ECO:0000269|PubMed:22963728};
DE Flags: Precursor;
OS Lachesis muta (South American bushmaster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Lachesis.
OX NCBI_TaxID=8752;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-59, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=22963728; DOI=10.1016/j.toxicon.2012.08.008;
RA Bregge-Silva C., Nonato M.C., de Albuquerque S., Ho P.L.,
RA Junqueira de Azevedo I.L., Vasconcelos Diniz M.R., Lomonte B., Rucavado A.,
RA Diaz C., Gutierrez J.M., Arantes E.C.;
RT "Isolation and biochemical, functional and structural characterization of a
RT novel l-amino acid oxidase from Lachesis muta snake venom.";
RL Toxicon 60:1263-1276(2012).
RN [2]
RP PROTEIN SEQUENCE OF 19-42, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=18541473; DOI=10.1016/j.jprot.2007.10.004;
RA Sanz L., Escolano J., Ferretti M., Biscoglio M.J., Rivera E.,
RA Crescenti E.J., Angulo Y., Lomonte B., Gutierrez J.M., Calvete J.J.;
RT "Snake venomics of the South and Central American Bushmasters. Comparison
RT of the toxin composition of Lachesis muta gathered from proteomic versus
RT transcriptomic analysis.";
RL J. Proteomics 71:46-60(2008).
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:22963728). Is highly active on L-Met=L-Leu>>L-Phe>L-
CC Trp>L-Tyr>L-Ile, and weakly or not active on L-His, L-Arg, L-Val, L-
CC Gln, L-Thr, L-Lys, and L-Ser (PubMed:22963728). Exhibits a low
CC myotoxicity (a mild myonecrosis is observed after injection in mice
CC quadriceps muscle) (PubMed:22963728). In vitro, is cytotoxic to a lot
CC of human cell lines, including AGS (IC(50)=22.7 ug/ml), MCF-7
CC (IC(50)=1.4 ug/ml), HL-60, HeLa and Jurkat cells, as well as to the
CC parasite Leishmania brasiliensis (IC(50)=2.22 ug/ml) (PubMed:22963728).
CC This cytotoxicity is dependent on the production of hydrogen peroxyde,
CC since it is inhibited by catalase, a hydrogen peroxyde scavenger
CC (PubMed:22963728). {ECO:0000269|PubMed:22963728}.
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:22963728};
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:22963728};
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:22963728};
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:22963728};
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:22963728};
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:22963728};
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:22963728};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000305|PubMed:22963728};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.97 mM for L-Leu {ECO:0000269|PubMed:22963728};
CC Vmax=0.063 umol/min/mg enzyme for L-Leu
CC {ECO:0000269|PubMed:22963728};
CC pH dependence:
CC Optimum pH is 8.0 for L-Leu. {ECO:0000269|PubMed:22963728};
CC Temperature dependence:
CC Optimum temperature is 4 degrees Celsius.
CC {ECO:0000269|PubMed:22963728};
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:P81382}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22963728}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:22963728}.
CC -!- MASS SPECTROMETRY: Mass=60852; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:22963728};
CC -!- MISCELLANEOUS: This enzyme does not cause hemorrhage, paw edema
CC morphological changes of heart, lung and kidney when injected into
CC mice. Is not toxic to the parasite Trypanosoma cruzi.
CC {ECO:0000269|PubMed:22963728}.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC subfamily. {ECO:0000250|UniProtKB:B0VXW0}.
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DR EMBL; JX171244; AFP89360.1; -; mRNA.
DR AlphaFoldDB; J7H670; -.
DR SMR; J7H670; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0106329; F:L-phenylalaine oxidase activity; IEA:RHEA.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002937; Amino_oxidase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01593; Amino_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; FAD; Flavoprotein; Glycoprotein;
KW Myotoxin; Oxidoreductase; Secreted; Signal; Toxin.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:22963728"
FT CHAIN 19..516
FT /note="L-amino acid oxidase Lm29"
FT /id="PRO_0000430750"
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|PROSITE-ProRule:PRU00498"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 28..191
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT DISULFID 349..430
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT CONFLICT 57
FT /note="Missing (in Ref. 1; AA sequence)"
SQ SEQUENCE 516 AA; 58532 MW; 1977DF6C51F1C17B CRC64;
MNVFFMFSLL FLAALGSCAD DRNPLGECFR ETDYEEFLEI AKNGLRATSN PKHVVIVGAG
MSGLSAAYVL AEAGHQVTVL EASERAGGRV RTYRNDKEGW YANLGPMRLP EKHRIVREYI
RKFGLQLNEF HQENDNAWHF IKNIRKRVGE VKEDPGLLQY PVKPSEEGKS AGQLYEESLG
KVAEELKRTN CSYILNKYDT YSTKEYLLKE GNLSPGAVDM IGDLLNEDSG YYVSFIESLK
HDDIFGYEKR FDEIVDGMDK LPTSMYQAIK EKVRFNARVI KIQQNDREVT VTYQTSANEM
SPVTADYVIV CTTSRATRRI TFEPPLPPKK AHALRSVHYR SGTKIFLTCT KKFWEDDGIR
GGKSTTDLPS RFIYYPNHNF TSGVGVIIAY GIGDDANFFQ ALDFKDCGDI VINDLSLIHQ
LPKKDIQTFC YPSMIQRWSL DKYAMGGITT FTPYQFQHFS EALTAPFKRI YFAGEYTAQF
HGWIDSTIKS GLTAARDVNR ASENPSGIHL SNDNEL
