MAO2_BACSU
ID MAO2_BACSU Reviewed; 582 AA.
AC P45868;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=NAD-dependent malic enzyme 2 {ECO:0000305};
DE Short=NAD-ME 2;
DE EC=1.1.1.38 {ECO:0000269|PubMed:12949160, ECO:0000269|PubMed:16788182};
DE AltName: Full=Malate dehydrogenase MaeA {ECO:0000305};
DE AltName: Full=Malic enzyme A {ECO:0000303|PubMed:12949160};
GN Name=maeA {ECO:0000303|PubMed:12949160}; Synonyms=ywkA;
GN OrderedLocusNames=BSU37050;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9353933; DOI=10.1099/00221287-143-10-3313;
RA Presecan E., Moszer I., Boursier L., Cruz Ramos H., De La Fuente V.,
RA Hullo M.-F., Lelong C., Schleich S., Sekowska A., Song B.H., Villani G.,
RA Kunst F., Danchin A., Glaser P.;
RT "The Bacillus subtilis genome from gerBC (311 degrees) to licR (334
RT degrees).";
RL Microbiology 143:3313-3328(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12949160; DOI=10.1099/mic.0.26256-0;
RA Doan T., Servant P., Tojo S., Yamaguchi H., Lerondel G., Yoshida K.,
RA Fujita Y., Aymerich S.;
RT "The Bacillus subtilis ywkA gene encodes a malic enzyme and its
RT transcription is activated by the YufL/YufM two-component system in
RT response to malate.";
RL Microbiology 149:2331-2343(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=168;
RX PubMed=16788182; DOI=10.1128/jb.00167-06;
RA Lerondel G., Doan T., Zamboni N., Sauer U., Aymerich S.;
RT "YtsJ has the major physiological role of the four paralogous malic enzyme
RT isoforms in Bacillus subtilis.";
RL J. Bacteriol. 188:4727-4736(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=23136871; DOI=10.1111/1574-6968.12041;
RA Meyer F.M., Stuelke J.;
RT "Malate metabolism in Bacillus subtilis: distinct roles for three classes
RT of malate-oxidizing enzymes.";
RL FEMS Microbiol. Lett. 339:17-22(2013).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=33824210; DOI=10.1128/mbio.03438-20;
RA Hoerl M., Fuhrer T., Zamboni N.;
RT "Bifunctional malic/malolactic enzyme provides a novel mechanism for NADPH-
RT balancing in Bacillus subtilis.";
RL MBio 12:0-0(2021).
CC -!- FUNCTION: Catalyzes the decarboxylation of malate to pyruvate
CC (PubMed:12949160, PubMed:16788182). Can use NAD and NADP, but with a
CC strong preference for NAD (PubMed:12949160, PubMed:16788182). Can also
CC catalyze the decarboxylation of oxaloacetate (PubMed:16788182).
CC Involved in keeping the ATP levels high (PubMed:23136871).
CC {ECO:0000269|PubMed:12949160, ECO:0000269|PubMed:16788182,
CC ECO:0000269|PubMed:23136871}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate + NAD(+) = CO2 + NADH + pyruvate;
CC Xref=Rhea:RHEA:12653, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.38;
CC Evidence={ECO:0000269|PubMed:12949160, ECO:0000269|PubMed:16788182};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxaloacetate = CO2 + pyruvate; Xref=Rhea:RHEA:15641,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16526; EC=1.1.1.38;
CC Evidence={ECO:0000269|PubMed:16788182};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P76558};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P76558};
CC Note=Divalent metal cations. {ECO:0000250|UniProtKB:P76558};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.6 mM for malate {ECO:0000269|PubMed:12949160};
CC KM=3.95 mM for malate {ECO:0000269|PubMed:16788182};
CC KM=1.1 mM for NAD {ECO:0000269|PubMed:12949160};
CC KM=5.3 mM for NAP {ECO:0000269|PubMed:16788182};
CC KM=9.0 mM for NADP {ECO:0000269|PubMed:12949160};
CC KM=6.7 mM for NADP {ECO:0000269|PubMed:16788182};
CC -!- INDUCTION: Induced in the presence of malate via the two-component
CC system MalK/MalR. The regulator MalR binds to the promoter region of
CC maeA. Is not subject to carbon catabolite repression.
CC {ECO:0000269|PubMed:12949160}.
CC -!- DISRUPTION PHENOTYPE: Mutant can use malate, succinate plus glutamate
CC or glucose as efficiently as the wild-type strain (PubMed:12949160,
CC PubMed:16788182). The ATP concentrations in the mutant grown in minimal
CC medium with glucose are similar to the wild-type level. ATP
CC concentrations decrease by about 10% in malate minimal medium. The
CC mleA-maeA-malS triple mutant shows a decrease in ATP concentrations by
CC about 20% and a moderate growth defect (PubMed:23136871). NADPH
CC overproduction is roughly halved in the deletion mutant
CC (PubMed:33824210). {ECO:0000269|PubMed:12949160,
CC ECO:0000269|PubMed:16788182, ECO:0000269|PubMed:23136871,
CC ECO:0000269|PubMed:33824210}.
CC -!- SIMILARITY: Belongs to the malic enzymes family. {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; Z49782; CAA89880.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB15722.1; -; Genomic_DNA.
DR PIR; S55433; S55433.
DR RefSeq; NP_391586.1; NC_000964.3.
DR RefSeq; WP_003227639.1; NC_000964.3.
DR AlphaFoldDB; P45868; -.
DR SMR; P45868; -.
DR STRING; 224308.BSU37050; -.
DR PaxDb; P45868; -.
DR PRIDE; P45868; -.
DR EnsemblBacteria; CAB15722; CAB15722; BSU_37050.
DR GeneID; 937045; -.
DR KEGG; bsu:BSU37050; -.
DR PATRIC; fig|224308.43.peg.3884; -.
DR eggNOG; COG0281; Bacteria.
DR InParanoid; P45868; -.
DR OMA; ADHKVYF; -.
DR PhylomeDB; P45868; -.
DR BioCyc; BSUB:BSU37050-MON; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; IEA:UniProtKB-EC.
DR GO; GO:0004470; F:malic enzyme activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.10380; -; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR015884; Malic_enzyme_CS.
DR InterPro; IPR012301; Malic_N_dom.
DR InterPro; IPR037062; Malic_N_dom_sf.
DR InterPro; IPR012302; Malic_NAD-bd.
DR InterPro; IPR001891; Malic_OxRdtase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00390; malic; 1.
DR Pfam; PF03949; Malic_M; 1.
DR PIRSF; PIRSF000106; ME; 1.
DR PRINTS; PR00072; MALOXRDTASE.
DR SMART; SM01274; malic; 1.
DR SMART; SM00919; Malic_M; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00331; MALIC_ENZYMES; 1.
PE 1: Evidence at protein level;
KW Magnesium; Manganese; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..582
FT /note="NAD-dependent malic enzyme 2"
FT /id="PRO_0000160209"
FT ACT_SITE 122
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT BINDING 266
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT BINDING 267
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT BINDING 290
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT BINDING 323..326
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT BINDING 439
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40927"
FT BINDING 484
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40927"
SQ SEQUENCE 582 AA; 64103 MW; E02821E341C20302 CRC64;
MGYYLTWLTI SRKKEICLNN IKKTKEGHLE TTLRGKEVLS IPTLNKGVAF SLEERQELGL
EGLLPPTVLS LDQQAQRAYE QFQAQPDRLR QNVYLSDLAN RNEVLFYKLL KNHLREMLPV
VYTPTVGEAI QEYSHEYRRP QGIYLSIDNI DGIEKAFENL HATAGDIDLI VATDSESILG
IGDWGVGGIN IAIGKLAVYT AAAGIDPSRV IPVVLDVGTN NEKLLNDPLY IGNKHERVQG
ERYEAFIDAY VKAALKFFPK ALLHWEDLGN KNARNIMKKY NHEILTFNDD IQGTGAITLA
GVLAAMKKTG ASIKDQRVVI FGAGSAGIGI ADQIRDTMVL AGLSEEEANK RFYTLDYRGL
LTEDIEGILD FQKPYLRNAD EVKDWKRDEK GQIPFDEVVR QAKPTILIGT SGVSGAFTEE
IVKEMASHVD RPVIMPMSNP THLAEAVPED LFKWTDGKVL IATGSPFDNV EYNGVSYEIG
QSNNAFAFPG LGLGSIVAEA RIITPAMFAA TADAIAEMVD LETPGAGLLP SIDKLQEVSI
QVAIAVAEAA IKDGVANRQP EDVKQAVLDA MWTPEYKKVI AK
