NDH_STAA8
ID NDH_STAA8 Reviewed; 402 AA.
AC Q2FZV7;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Type II NADH:quinone oxidoreductase {ECO:0000303|PubMed:25849513};
DE EC=1.6.5.9 {ECO:0000269|PubMed:26172206, ECO:0000269|PubMed:28801048, ECO:0000269|PubMed:29524843};
DE AltName: Full=NDH-2 {ECO:0000303|PubMed:26172206};
GN OrderedLocusNames=SAOUHSC_00878;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP COFACTOR, SUBUNIT, SUBCELLULAR LOCATION, AND CRYSTALLIZATION.
RC STRAIN=NCTC 8325 / PS 47;
RX PubMed=25849513; DOI=10.1107/s2053230x15005178;
RA Rosario A.L., Sena F.V., Batista A.P., Oliveira T.F., Athayde D.,
RA Pereira M.M., Brito J.A., Archer M.;
RT "Expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of a type II NADH:quinone oxidoreductase from the
RT human pathogen Staphylococcus aureus.";
RL Acta Crystallogr. F Struct. Biol. Commun. 71:477-482(2015).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND DOMAIN.
RC STRAIN=NCTC 8325 / PS 47;
RX PubMed=26172206; DOI=10.1111/mmi.13120;
RA Sena F.V., Batista A.P., Catarino T., Brito J.A., Archer M., Viertler M.,
RA Madl T., Cabrita E.J., Pereira M.M.;
RT "Type-II NADH:quinone oxidoreductase from Staphylococcus aureus has two
RT distinct binding sites and is rate limited by quinone reduction.";
RL Mol. Microbiol. 98:272-288(2015).
RN [4]
RP REACTION MECHANISM, ACTIVE SITE, AND DOMAIN.
RX PubMed=28181562; DOI=10.1038/srep42303;
RA Marreiros B.C., Sena F.V., Sousa F.M., Oliveira A.S., Soares C.M.,
RA Batista A.P., Pereira M.M.;
RT "Structural and functional insights into the catalytic mechanism of the
RT type II NADH:quinone oxidoreductase family.";
RL Sci. Rep. 7:42303-42303(2017).
RN [5]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC STRAIN=NCTC 8325 / PS 47;
RX PubMed=29524843; DOI=10.1016/j.redox.2018.02.004;
RA Sena F.V., Sousa F.M., Oliveira A.S.F., Soares C.M., Catarino T.,
RA Pereira M.M.;
RT "Regulation of the mechanism of Type-II NADH: Quinone oxidoreductase from
RT S. aureus.";
RL Redox Biol. 16:209-214(2018).
RN [6] {ECO:0007744|PDB:5NA1, ECO:0007744|PDB:5NA4}
RP X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF WILD-TYPE AND MUTANT SER-172 IN
RP COMPLEXES WITH FAD, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVE SITE,
RP AND MUTAGENESIS OF GLU-172.
RC STRAIN=NCTC 8325 / PS 47;
RX PubMed=28801048; DOI=10.1016/j.bbabio.2017.08.002;
RA Sousa F.M., Sena F.V., Batista A.P., Athayde D., Brito J.A., Archer M.,
RA Oliveira A.S.F., Soares C.M., Catarino T., Pereira M.M.;
RT "The key role of glutamate 172 in the mechanism of type II NADH:quinone
RT oxidoreductase of Staphylococcus aureus.";
RL Biochim. Biophys. Acta 1858:823-832(2017).
CC -!- FUNCTION: Alternative, nonproton pumping NADH:quinone oxidoreductase
CC that delivers electrons to the respiratory chain by oxidation of NADH
CC and reduction of quinones, and contributes to the regeneration of
CC NAD(+) (PubMed:26172206, PubMed:28801048). Can use DMN, a menaquinone
CC analog, 2,3-dimethoxy-5,6-dimethyl-benzoquinone (DDB), an ubiquinone
CC analog, or 2,3,5,6-tetramethyl-1,4-benzoquinone (Duroquinone, DQ) a
CC plastoquinone analog as electron acceptors (PubMed:26172206).
CC {ECO:0000269|PubMed:26172206, ECO:0000269|PubMed:28801048}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADH = a quinol + NAD(+);
CC Xref=Rhea:RHEA:46160, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132124; EC=1.6.5.9;
CC Evidence={ECO:0000269|PubMed:26172206, ECO:0000269|PubMed:28801048,
CC ECO:0000269|PubMed:29524843};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a menaquinone + H(+) + NADH = a menaquinol + NAD(+);
CC Xref=Rhea:RHEA:29235, Rhea:RHEA-COMP:9537, Rhea:RHEA-COMP:9539,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16374, ChEBI:CHEBI:18151,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:26172206};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ubiquinone + H(+) + NADH = a ubiquinol + NAD(+);
CC Xref=Rhea:RHEA:23152, Rhea:RHEA-COMP:9565, Rhea:RHEA-COMP:9566,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:26172206};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:25849513, ECO:0000269|PubMed:26172206,
CC ECO:0000269|PubMed:28801048};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:26172206,
CC ECO:0000269|PubMed:28801048};
CC -!- ACTIVITY REGULATION: Inhibited by HQNO, a quinone derivative.
CC {ECO:0000269|PubMed:26172206, ECO:0000269|PubMed:29524843}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=69.9 uM for DMN {ECO:0000269|PubMed:26172206};
CC KM=63.7 uM for DDB {ECO:0000269|PubMed:26172206};
CC KM=55.4 uM for DQ {ECO:0000269|PubMed:26172206};
CC KM=20.5 uM for NADH {ECO:0000269|PubMed:26172206};
CC Vmax=132.7 umol/min/mg enzyme with DMN as substrate
CC {ECO:0000269|PubMed:26172206};
CC Vmax=129.3 umol/min/mg enzyme with DDB as substrate
CC {ECO:0000269|PubMed:26172206};
CC Vmax=119.1 umol/min/mg enzyme with DQ as substrate
CC {ECO:0000269|PubMed:26172206};
CC Vmax=175.9 umol/min/mg enzyme with NADH as substrate
CC {ECO:0000269|PubMed:26172206};
CC Note=kcat is 67.9 sec(-1) with DMN as substrate. kcat is 69.4 sec(-1)
CC with DDB as substrate. kcat is 68.2 sec(-1) with DQ as substrate.
CC {ECO:0000269|PubMed:26172206};
CC -!- SUBUNIT: Homodimer in solution (PubMed:25849513, PubMed:26172206).
CC Forms homotetramers; dimer of dimers (PubMed:25849513,
CC PubMed:26172206). {ECO:0000269|PubMed:25849513,
CC ECO:0000269|PubMed:26172206}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25849513,
CC ECO:0000269|PubMed:26172206}. Note=Interacts with the membrane via an
CC anti-parallel three-stranded beta-sheet followed by two helices
CC arranged in a helix-turn-helix motif at the C-terminal region.
CC {ECO:0000269|PubMed:26172206}.
CC -!- DOMAIN: Contains a first dinucleotide binding domain, which harbors
CC FAD, a second dinucleotide binding domain, which interacts with NADH
CC and C-terminal domain that provides anchoring to the membrane
CC (PubMed:28801048). A long discussion has taken place about whether NADH
CC and the quinone bind to the same or to different sites. Structural
CC studies clearly indicate the presence of distinct binding sites for the
CC two substrates (PubMed:26172206, PubMed:28181562).
CC {ECO:0000269|PubMed:26172206, ECO:0000269|PubMed:28181562,
CC ECO:0000269|PubMed:28801048}.
CC -!- SIMILARITY: Belongs to the NADH dehydrogenase family. {ECO:0000305}.
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DR EMBL; CP000253; ABD30003.1; -; Genomic_DNA.
DR RefSeq; WP_000046076.1; NZ_LS483365.1.
DR RefSeq; YP_499431.1; NC_007795.1.
DR PDB; 5NA1; X-ray; 2.32 A; A=1-402.
DR PDB; 5NA4; X-ray; 2.55 A; A=1-402.
DR PDBsum; 5NA1; -.
DR PDBsum; 5NA4; -.
DR AlphaFoldDB; Q2FZV7; -.
DR SMR; Q2FZV7; -.
DR STRING; 1280.SAXN108_0936; -.
DR EnsemblBacteria; ABD30003; ABD30003; SAOUHSC_00878.
DR GeneID; 3919225; -.
DR KEGG; sao:SAOUHSC_00878; -.
DR PATRIC; fig|93061.5.peg.798; -.
DR eggNOG; COG1252; Bacteria.
DR HOGENOM; CLU_021377_7_2_9; -.
DR OMA; DHCIFLD; -.
DR PRO; PR:Q2FZV7; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003955; F:NAD(P)H dehydrogenase (quinone) activity; IBA:GO_Central.
DR GO; GO:0050136; F:NADH dehydrogenase (quinone) activity; IEA:RHEA.
DR GO; GO:0019646; P:aerobic electron transport chain; IBA:GO_Central.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; FAD; Flavoprotein; Membrane; NAD;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..402
FT /note="Type II NADH:quinone oxidoreductase"
FT /id="PRO_0000287371"
FT ACT_SITE 172
FT /evidence="ECO:0000305|PubMed:28181562,
FT ECO:0000305|PubMed:28801048"
FT BINDING 12..16
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28801048"
FT BINDING 39..40
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28801048"
FT BINDING 83
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28801048"
FT BINDING 302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28801048"
FT BINDING 319..320
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28801048"
FT BINDING 379
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28801048"
FT MUTAGEN 172
FT /note="E->A: 3.4-fold decrease in kcat for DMN. Decreases
FT the overall affinity for NAD(+) and the quinone."
FT /evidence="ECO:0000269|PubMed:28801048"
FT MUTAGEN 172
FT /note="E->D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:28801048"
FT MUTAGEN 172
FT /note="E->Q: 12-fold decrease in kcat for DMN. Decreases
FT the overall affinity for NAD(+) and the quinone."
FT /evidence="ECO:0000269|PubMed:28801048"
FT MUTAGEN 172
FT /note="E->S: 6-fold decrease in kcat for DMN. Decreases the
FT overall affinity for NAD(+) and the quinone."
FT /evidence="ECO:0000269|PubMed:28801048"
FT STRAND 6..11
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 15..27
FT /evidence="ECO:0007829|PDB:5NA1"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 33..45
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 50..55
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:5NA1"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:5NA1"
FT TURN 88..91
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 131..150
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 168..188
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 212..224
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 242..247
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 270..274
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 319..337
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:5NA4"
FT STRAND 361..365
FT /evidence="ECO:0007829|PDB:5NA1"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:5NA1"
FT HELIX 373..399
FT /evidence="ECO:0007829|PDB:5NA1"
SQ SEQUENCE 402 AA; 44104 MW; 2C3DE4D5098C2D53 CRC64;
MAQDRKKVLV LGAGYAGLQT VTKLQKAIST EEAEITLINK NEYHYEATWL HEASAGTLNY
EDVLYPVESV LKKDKVNFVQ AEVTKIDRDA KKVETNQGIY DFDILVVALG FVSETFGIEG
MKDHAFQIEN VITARELSRH IEDKFANYAA SKEKDDNDLS ILVGGAGFTG VEFLGELTDR
IPELCSKYGV DQNKVKITCV EAAPKMLPMF SEELVNHAVS YLEDRGVEFK IATPIVACNE
KGFVVEVDGE KQQLNAGTSV WAAGVRGSKL MEESFEGVKR GRIVTKQDLT INGYDNIFVI
GDCSAFIPAG EERPLPTTAQ IAMQQGESVA KNIKRILNGE STEEFEYVDR GTVCSLGSHD
GVGMVFGKPI AGKKAAFMKK VIDTRAVFKI GGIGLAFKKG KF
