ID   NAOX_LACLM              Reviewed;         446 AA.
AC   A2RIB7; P81759; Q8KR34;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   27-MAR-2024, entry version 92.
DE   RecName: Full=NADH oxidase;
DE            Short=NOXase;
DE            EC=1.6.3.4 {ECO:0000269|Ref.3};
GN   Name=noxE {ECO:0000312|EMBL:CAL97012.1}; OrderedLocusNames=llmg_0408;
OS   Lactococcus lactis subsp. cremoris (strain MG1363).
OC   Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae;
OC   Lactococcus; Lactococcus cremoris subsp. cremoris.
OX   NCBI_TaxID=416870;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11932446; DOI=10.1099/00221287-148-4-1003;
RA   Hoefnagel M.H.N., Starrenburg M.J.C., Martens D.E., Hugenholtz J.,
RA   Kleerebezem M., Van Swam I.I., Bongers R., Westerhoff H.V., Snoep J.L.;
RT   "Metabolic engineering of lactic acid bacteria, the combined approach:
RT   kinetic modelling, metabolic control and experimental analysis.";
RL   Microbiology 148:1003-1013(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MG1363;
RX   PubMed=17307855; DOI=10.1128/jb.01768-06;
RA   Wegmann U., O'Connell-Motherway M., Zomer A., Buist G., Shearman C.,
RA   Canchaya C., Ventura M., Goesmann A., Gasson M.J., Kuipers O.P.,
RA   van Sinderen D., Kok J.;
RT   "The complete genome sequence of the lactic acid bacterial paradigm
RT   Lactococcus lactis subsp. cremoris MG1363.";
RL   J. Bacteriol. 189:3256-3270(2007).
RN   [3] {ECO:0000305}
RP   PROTEIN SEQUENCE OF 1-25, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX   AGRICOLA=IND23261759; DOI=10.1016/S0958-6946(01)00031-0;
RA   Lopez de Felipe F., Hugenholtz J.;
RT   "Purification and characterisation of the water forming NADH-oxidase from
RT   Lactococcus lactis.";
RL   Int. Dairy J. 11:37-44(2001).
CC   -!- FUNCTION: Catalyzes the four-electron reduction of molecular oxygen to
CC       water. Active on beta-NADH, but not on alpha-NADH, beta-NADPH or alpha-
CC       NADPH. Under aerobic conditions, oxygen acts as the electron acceptor.
CC       Under anaerobic conditions, DCIP and MB can replace oxygen as the
CC       electron acceptor. {ECO:0000269|Ref.3}.
CC   -!- CATALYTIC ACTIVITY: [NADH oxidase]:
CC       Reaction=2 H(+) + 2 NADH + O2 = 2 H2O + 2 NAD(+); Xref=Rhea:RHEA:37799,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.3.4;
CC         Evidence={ECO:0000269|Ref.3};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|Ref.3};
CC       Note=Binds 1 FAD per subunit. {ECO:0000269|Ref.3};
CC   -!- ACTIVITY REGULATION: Inhibited by hydrogen peroxide, sulfhydryl
CC       reagents and quinine, but not by EDTA. {ECO:0000269|Ref.3}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=4.1 uM for beta-NADH (in the presence of oxygen)
CC         {ECO:0000269|Ref.3};
CC         Vmax=83 umol/min/mg enzyme toward beta-NADH (in the presence of
CC         oxygen) {ECO:0000269|Ref.3};
CC       pH dependence:
CC         Optimum pH is 6.0-9.0. Below pH 6.0 the enzyme is reversibly
CC         inactivated, above pH 10.0 the enzyme is irreversibly inactivated.
CC         {ECO:0000269|Ref.3};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.3}.
CC   -!- SIMILARITY: Belongs to the class-III pyridine nucleotide-disulfide
CC       oxidoreductase family. {ECO:0000255}.
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DR   EMBL; AY046926; AAL02357.1; -; Genomic_DNA.
DR   EMBL; AM406671; CAL97012.1; -; Genomic_DNA.
DR   RefSeq; WP_011834457.1; NZ_WJVF01000001.1.
DR   AlphaFoldDB; A2RIB7; -.
DR   SMR; A2RIB7; -.
DR   STRING; 416870.llmg_0408; -.
DR   GeneID; 61108710; -.
DR   KEGG; llm:llmg_0408; -.
DR   eggNOG; COG0446; Bacteria.
DR   HOGENOM; CLU_003291_1_0_9; -.
DR   OrthoDB; 9802028at2; -.
DR   PhylomeDB; A2RIB7; -.
DR   BRENDA; 1.6.3.4; 2903.
DR   SABIO-RK; A2RIB7; -.
DR   Proteomes; UP000000364; Chromosome.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IEA:UniProtKB-EC.
DR   Gene3D; 3.30.390.30; -; 1.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR023753; FAD/NAD-binding_dom.
DR   InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR   InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR   PANTHER; PTHR43429:SF1; COENZYME A DISULFIDE REDUCTASE; 1.
DR   PANTHER; PTHR43429; PYRIDINE NUCLEOTIDE-DISULFIDE OXIDOREDUCTASE DOMAIN-CONTAINING; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   Pfam; PF02852; Pyr_redox_dim; 1.
DR   PRINTS; PR00368; FADPNR.
DR   PRINTS; PR00411; PNDRDTASEI.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR   SUPFAM; SSF55424; FAD/NAD-linked reductases, dimerisation (C-terminal) domain; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; FAD; Flavoprotein; NAD; Oxidation;
KW   Oxidoreductase; Redox-active center.
FT   CHAIN           1..446
FT                   /note="NADH oxidase"
FT                   /id="PRO_0000292941"
FT   ACT_SITE        10
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   ACT_SITE        42
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         7..11
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         32
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   BINDING         42
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         79
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   BINDING         109..112
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         131
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   BINDING         158
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   BINDING         159
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         178
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         187
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         244
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         282
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         298
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         299
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   BINDING         300
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         301
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   BINDING         329
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P37062"
FT   BINDING         427
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   MOD_RES         42
FT                   /note="Cysteine sulfinic acid (-SO2H)"
FT                   /evidence="ECO:0000250|UniProtKB:Q5XC60"
FT   CONFLICT        11
FT                   /note="A -> AA (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   446 AA;  48872 MW;  1B1FA2FE313D6C03 CRC64;
     MKIVVIGTNH AGIATANTLL EQYPGHEIVM IDRNSNMSYL GCGTAIWVGR QIEKPDELFY
     AKAEDFEAKG VKILTETEVS EIDFANKKVY AKTKSDDEII EAYDKLVLAT GSRPIIPNLP
     GKDLKGIHFL KLFQEGQAID AEFAKEKVKR IAVIGAGYIG TEIAEAAKRR GKEVLLFDAE
     NTSLASYYDE EFAKGMDENL AQHGIELHFG ELAKEFKANE EGYVSQIVTN KATYDVDLVI
     NCIGFTANSA LASDKLATFK NGAIKVDKHQ QSSDPDVYAV GDVATIYSNA LQDFTYIALA
     SNAVRSGIVA GHNIGGKELE SVGVQGSNGI SIFGYNMTST GLSVKAAKKL GLEVSFSDFE
     DKQKAWFLHE NNDSVKIRIV YETKSRRIIG AQLASKSEII AGNINMFSLA IQEKKTIDEL
     ALLDLFFLPH FNSPYNYMTV AALNAK
//