OXLA_OPHHA
ID OXLA_OPHHA Reviewed; 491 AA.
AC P81383; A8QL50;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 3.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=L-amino-acid oxidase {ECO:0000303|PubMed:2044840};
DE Short=LAO;
DE Short=Oh-LAAO {ECO:0000303|PubMed:17543361};
DE EC=1.4.3.2 {ECO:0000269|PubMed:17543361, ECO:0000269|PubMed:2044840};
DE Flags: Precursor;
OS Ophiophagus hannah (King cobra) (Naja hannah).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Ophiophagus.
OX NCBI_TaxID=8665;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 21-45; 121-129; 189-195;
RP 272-278 AND 428-439, IDENTIFICATION BY MASS SPECTROMETRY, GLYCOSYLATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=17543361; DOI=10.1016/j.toxicon.2007.04.013;
RA Jin Y., Lee W.-H., Zeng L., Zhang Y.;
RT "Molecular characterization of L-amino acid oxidase from king cobra
RT venom.";
RL Toxicon 50:479-489(2007).
RN [2]
RP PROTEIN SEQUENCE OF 21-39, SUBUNIT, GLYCOSYLATION, AND COFACTOR.
RC TISSUE=Venom;
RX PubMed=8080286; DOI=10.1006/abbi.1994.1401;
RA Ponnudurai G., Chung M.C.M., Tan N.-H.;
RT "Purification and properties of the L-amino acid oxidase from Malayan pit
RT viper (Calloselasma rhodostoma) venom.";
RL Arch. Biochem. Biophys. 313:373-378(1994).
RN [3]
RP PROTEIN SEQUENCE OF 21-35, FUNCTION, SUBUNIT, AND GLYCOSYLATION.
RC TISSUE=Venom;
RX PubMed=9304806; DOI=10.1016/s1357-2725(97)00024-1;
RA Ahn M.Y., Lee B.M., Kim Y.S.;
RT "Characterization and cytotoxicity of L-amino acid oxidase from the venom
RT of king cobra (Ophiophagus hannah).";
RL Int. J. Biochem. Cell Biol. 29:911-919(1997).
RN [4]
RP FUNCTION, COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION,
RP AND TOXIC DOSE.
RX PubMed=2619759;
RA Tan N.H., Saifuddin M.N.;
RT "Isolation and characterization of an unusual form of L-amino acid oxidase
RT from King cobra (Ophiophagus hannah) venom.";
RL Biochem. Int. 19:937-944(1989).
RN [5]
RP FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2044840; DOI=10.1016/0020-711x(91)90114-3;
RA Tan N.H., Saifuddin M.N.;
RT "Substrate specificity of king cobra (Ophiophagus hannah) venom L-amino
RT acid oxidase.";
RL Int. J. Biochem. 23:323-327(1991).
RN [6]
RP ISOFORM.
RA Tan N.-H., Choy S.-K.;
RT "The edema inducing activity of Ophiophagus hannah (king cobra) venom L-
RT amino acid oxidase.";
RL Toxicon 32:539-539(1994).
RN [7]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=7886693; DOI=10.1016/0041-0101(94)90407-3;
RA Li Z.Y., Yu T.F., Lian E.C.;
RT "Purification and characterization of L-amino acid oxidase from king cobra
RT (Ophiophagus hannah) venom and its effects on human platelet aggregation.";
RL Toxicon 32:1349-1358(1994).
RN [8]
RP FUNCTION, AND ANTIBACTERIAL ACTIVITY.
RC TISSUE=Venom;
RX PubMed=21059402; DOI=10.1016/j.cbpc.2010.11.001;
RA Lee M.L., Tan N.H., Fung S.Y., Sekaran S.D.;
RT "Antibacterial action of a heat-stable form of L-amino acid oxidase
RT isolated from king cobra (Ophiophagus hannah) venom.";
RL Comp. Biochem. Physiol. 153:237-242(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=24297900; DOI=10.1073/pnas.1314702110;
RA Vonk F.J., Casewell N.R., Henkel C.V., Heimberg A.M., Jansen H.J.,
RA McCleary R.J., Kerkkamp H.M., Vos R.A., Guerreiro I., Calvete J.J.,
RA Wuster W., Woods A.E., Logan J.M., Harrison R.A., Castoe T.A.,
RA de Koning A.P., Pollock D.D., Yandell M., Calderon D., Renjifo C.,
RA Currier R.B., Salgado D., Pla D., Sanz L., Hyder A.S., Ribeiro J.M.,
RA Arntzen J.W., van den Thillart G.E., Boetzer M., Pirovano W., Dirks R.P.,
RA Spaink H.P., Duboule D., McGlinn E., Kini R.M., Richardson M.K.;
RT "The king cobra genome reveals dynamic gene evolution and adaptation in the
RT snake venom system.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20651-20656(2013).
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:17543361, PubMed:2044840). Is very active against L-Lys,
CC L-Phe, L-Leu, L-Tyr, L-Trp, L-Arg, and L-Met, moderately active against
CC L-His, L-cystine, and L-Ile, and slightly active against L-Gln, L-Asn,
CC L-Ala, and L-Val (PubMed:2044840). L-Glu, L-Ser, L-Pro and Gly are
CC oxidized very slowly (PubMed:2044840). Its activity on platelet
CC aggregation is controversial. It has potent inhibitory activity on
CC platelet aggregation induced by ADP and the thromboxane analog U46619,
CC but not by thrombin, mucetin, ristocetin and stejnulxin
CC (PubMed:17543361), but it has also been shown to induce platelet
CC aggregation through the formation of hydrogen peroxide
CC (PubMed:7886693). It binds to bacteria and shows antibacterial
CC activities by generating hydrogen peroxide. Binding and antibacterial
CC activities are higher against Gram-positive than against Gram-negative
CC bacteria. May also have an ability to induce hemorrhage, hemolysis,
CC edema, apoptosis. {ECO:0000269|PubMed:17543361,
CC ECO:0000269|PubMed:2044840, ECO:0000269|PubMed:21059402,
CC ECO:0000269|PubMed:2619759, ECO:0000269|PubMed:7886693,
CC ECO:0000269|PubMed:9304806}.
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:17543361,
CC ECO:0000269|PubMed:2044840};
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:2044840};
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:2044840};
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:2044840};
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:2044840};
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:2044840};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-arginine + O2 = 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:2044840};
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:2044840};
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:2044840};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-cystine + O2 = (2R)-2-amino-2-carboxylatoethyl-
CC disulfanyl-oxopropanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:61284,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:35491, ChEBI:CHEBI:144484;
CC Evidence={ECO:0000269|PubMed:2044840};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-lysine + O2 = 6-amino-2-oxohexanoate + H2O2 + NH4(+);
CC Xref=Rhea:RHEA:14437, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:58183; Evidence={ECO:0000269|PubMed:2044840};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:2619759, ECO:0000269|PubMed:8080286};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.3 mM for L-His {ECO:0000269|PubMed:17543361};
CC KM=3.0 mM for L-His {ECO:0000269|PubMed:2044840};
CC KM=2.9 mM for L-Ile {ECO:0000269|PubMed:17543361};
CC KM=1.3 mM for L-Ile {ECO:0000269|PubMed:2044840};
CC KM=2.2 mM for L-Leu {ECO:0000269|PubMed:17543361};
CC KM=0.20 mM for L-Leu {ECO:0000269|PubMed:2044840};
CC KM=2.6 mM for L-Lys {ECO:0000269|PubMed:17543361};
CC KM=0.14 mM for L-Lys {ECO:0000269|PubMed:2044840};
CC KM=0.7 mM for L-Met {ECO:0000269|PubMed:17543361};
CC KM=0.01 mM for L-Tyr {ECO:0000269|PubMed:2044840};
CC KM=0.10 mM for L-Trp {ECO:0000269|PubMed:2044840};
CC KM=0.10 mM for L-Phe {ECO:0000269|PubMed:2044840};
CC KM=0.15 mM for L-Arg {ECO:0000269|PubMed:2044840};
CC KM=0.17 mM for L-ornithine {ECO:0000269|PubMed:2044840};
CC KM=0.35 mM for L-norleucine (L-2-aminohexanoate)
CC {ECO:0000269|PubMed:2044840};
CC KM=0.63 mM for L-Met {ECO:0000269|PubMed:2044840};
CC KM=0.67 mM for L-norvaline (L-2-aminopentanoate)
CC {ECO:0000269|PubMed:2044840};
CC KM=0.83 mM for L-cystine {ECO:0000269|PubMed:2044840};
CC KM=4.0 mM for L-Aminobutyric acid {ECO:0000269|PubMed:2044840};
CC KM=5.0 mM for L-Pro {ECO:0000269|PubMed:2044840};
CC KM=7.1 mM for L-Val {ECO:0000269|PubMed:2044840};
CC KM=7.8 mM for L-Glu {ECO:0000269|PubMed:2044840};
CC KM=12.5 mM for L-Ala {ECO:0000269|PubMed:2044840};
CC KM=20.0 mM for L-Gln {ECO:0000269|PubMed:2044840};
CC KM=22.2 mM for L-Asn {ECO:0000269|PubMed:2044840};
CC KM=28.6 mM for L-Ser {ECO:0000269|PubMed:2044840};
CC KM=31.0 mM for L-Gly {ECO:0000269|PubMed:2044840};
CC Temperature dependence:
CC Exhibits unusual thermal stability. At pH 7.4, the enzyme retains
CC full activity after incubation at 25 degrees Celsius for 30 days. Is
CC stable at alkaline condition and is not inactivated by freezing.
CC {ECO:0000269|PubMed:2619759};
CC -!- SUBUNIT: Homodimer; non-covalently linked. {ECO:0000269|PubMed:2044840,
CC ECO:0000269|PubMed:2619759, ECO:0000269|PubMed:8080286,
CC ECO:0000269|PubMed:9304806}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2044840}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2044840}.
CC -!- PTM: N-glycosylated. {ECO:0000305|PubMed:17543361,
CC ECO:0000305|PubMed:2619759, ECO:0000305|PubMed:8080286,
CC ECO:0000305|PubMed:9304806}.
CC -!- TOXIC DOSE: LD(50) is 5 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:2619759}.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: The existence of two isoforms has been reported, and could
CC explain the differences in sequence and kinetic parameters.
CC {ECO:0000305|Ref.6}.
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DR EMBL; EF080831; ABN72538.1; -; mRNA.
DR AlphaFoldDB; P81383; -.
DR SMR; P81383; -.
DR PRIDE; P81383; -.
DR TopDownProteomics; P81383; -.
DR BRENDA; 1.4.3.2; 4419.
DR SABIO-RK; P81383; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0001716; F:L-amino-acid oxidase activity; IDA:UniProtKB.
DR GO; GO:0050029; F:L-lysine oxidase activity; IEA:RHEA.
DR GO; GO:0106329; F:L-phenylalaine oxidase activity; IEA:RHEA.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
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.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0035821; P:modulation of process of another organism; IDA:UniProtKB.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002937; Amino_oxidase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR001613; Flavin_amine_oxidase.
DR Pfam; PF01593; Amino_oxidase; 1.
DR PRINTS; PR00757; AMINEOXDASEF.
DR SUPFAM; SSF51905; SSF51905; 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 inhibiting toxin; Secreted; Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:17543361,
FT ECO:0000269|PubMed:8080286, ECO:0000269|PubMed:9304806"
FT CHAIN 21..491
FT /note="L-amino-acid oxidase"
FT /evidence="ECO:0000305|PubMed:17543361,
FT ECO:0000305|PubMed:8080286, ECO:0000305|PubMed:9304806"
FT /id="PRO_0000099871"
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 269
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT BINDING 380
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 465
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT BINDING 472..477
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT BINDING 472..473
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..182
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT DISULFID 338..420
FT /evidence="ECO:0000250|UniProtKB:P81382"
FT CONFLICT 21
FT /note="H -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="C -> S (in Ref. 2; AA sequence and 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="W -> H (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 491 AA; 55977 MW; 2FD1E740BD73313E CRC64;
MNDFLLLLLV LFLGVPRSEN HVINLEECFQ EPEYENWLAT ASHGLTKTLN PKKIVIVGAG
ISGLTAAKLF REAGHEVVIL EASDRVGGRI KTHREDGWYV DVGPMRVPQT HRIVREYIKK
FNISLNPFRQ TDENAWYLIK HVRQKMSANN PENFGYQLNP NERGKSASQL FDETLDKVTD
DCTLQKEKYD SFSTKEYLIK EGKLSTGAVE MIGDFLNEEA GFHNSFLISV MDHFLFLNNS
FDEITGGFDQ LPERFFKDMD SIVHLNSTVE KIVHINNKVT VFYEGLSTNM RLVADYVLIT
ATARATRLIK FVPPLSIPKT RALRSLIYAS ATKIILVCTD KFWEKDGIHG GRSITDLPSR
VIYYPNHDFT NGIGVLLASY TWYSDSEFYT TLSDEKCVDV VMDDLVEIHN VSKDYLKSVC
GKHVVQKWAL DQYSMGAFST YTPYQITHYS QMLAQNEGRI YFAGEYTAHP HGWIETSMKS
AIREAINIHN A
