ID   MAO1_BACSU              Reviewed;         439 AA.
AC   P54572;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   02-SEP-2026, entry version 160.
DE   RecName: Full=NAD-dependent malic enzyme 1 {ECO:0000305};
DE            Short=NAD-ME 1;
DE            EC=1.1.1.38 {ECO:0000269|PubMed:16788182};
DE   AltName: Full=Malate dehydrogenase MleA {ECO:0000305};
GN   Name=mleA {ECO:0000303|PubMed:16788182}; Synonyms=yqkJ;
GN   OrderedLocusNames=BSU23550;
OS   Bacillus subtilis (strain 168).
OC   Bacteria; Bacillati; Bacillota; Bacilli; Caryophanales; Bacillaceae;
OC   Bacillus.
OX   NCBI_TaxID=224308;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=168 / JH642;
RX   PubMed=8969508; DOI=10.1099/13500872-142-11-3103;
RA   Mizuno M., Masuda S., Takemaru K., Hosono S., Sato T., Takeuchi M.,
RA   Kobayashi Y.;
RT   "Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the
RT   Bacillus subtilis genome containing the skin element and many sporulation
RT   genes.";
RL   Microbiology 142:3103-3111(1996).
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   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 432-439.
RX   PubMed=8501064; DOI=10.1128/jb.175.11.3607-3617.1993;
RA   Smith K., Bayer M.E., Youngman P.;
RT   "Physical and functional characterization of the Bacillus subtilis spoIIM
RT   gene.";
RL   J. Bacteriol. 175:3607-3617(1993).
RN   [4]
RP   DISCUSSION OF FUNCTION.
RX   PubMed=10903309; DOI=10.1074/jbc.m001112200;
RA   Wei Y., Guffanti A.A., Ito M., Krulwich T.A.;
RT   "Bacillus subtilis YqkI is a novel malic/Na+-lactate antiporter that
RT   enhances growth on malate at low protonmotive force.";
RL   J. Biol. Chem. 275:30287-30292(2000).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION, AND
RP   DISRUPTION 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   [6]
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   [7]
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. Is
CC       specific for NAD, cannot use NADP. Can also catalyze the
CC       decarboxylation of oxaloacetate (PubMed:16788182). Involved in keeping
CC       the ATP levels high (PubMed:23136871). {ECO:0000269|PubMed:16788182,
CC       ECO:0000269|PubMed:23136871}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate + NAD(+) = pyruvate + CO2 + NADH;
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:16788182};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=oxaloacetate + H(+) = pyruvate + CO2; 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=1.56 mM for malate {ECO:0000269|PubMed:16788182};
CC         KM=1 mM for NAD {ECO:0000269|PubMed:16788182};
CC   -!- INDUCTION: Weakly expressed in glucose or malate minimal medium.
CC       {ECO:0000269|PubMed:16788182}.
CC   -!- DISRUPTION PHENOTYPE: Mutant can use either a gluconeogenic carbon
CC       source or glucose as efficiently as the wild-type strain
CC       (PubMed:16788182). The ATP concentrations in the mutant grown in
CC       minimal medium with glucose are similar to the wild-type level. ATP
CC       concentrations slightly decrease in malate minimal medium. The mleA-
CC       maeA-malS triple mutant shows a decrease in ATP concentrations by about
CC       20% and a moderate growth defect (PubMed:23136871). NADPH
CC       overproduction is roughly halved in the deletion mutant
CC       (PubMed:33824210). {ECO:0000269|PubMed:16788182,
CC       ECO:0000269|PubMed:23136871, ECO:0000269|PubMed:33824210}.
CC   -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
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DR   EMBL; D84432; BAA12645.1; -; Genomic_DNA.
DR   EMBL; AL009126; CAB14287.1; -; Genomic_DNA.
DR   EMBL; L06664; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; C69967; C69967.
DR   RefSeq; NP_390236.1; NC_000964.3.
DR   RefSeq; WP_004398731.1; NC_000964.3.
DR   AlphaFoldDB; P54572; -.
DR   SMR; P54572; -.
DR   FunCoup; P54572; 301.
DR   STRING; 224308.BSU23550; -.
DR   jPOST; P54572; -.
DR   PaxDb; 224308-BSU23550; -.
DR   EnsemblBacteria; CAB14287; CAB14287; BSU_23550.
DR   GeneID; 938725; -.
DR   KEGG; bsu:BSU23550; -.
DR   PATRIC; fig|224308.179.peg.2567; -.
DR   eggNOG; COG0281; Bacteria.
DR   InParanoid; P54572; -.
DR   OrthoDB; 9805787at2; -.
DR   PhylomeDB; P54572; -.
DR   BioCyc; BSUB:BSU23550-MONOMER; -.
DR   Proteomes; UP000001570; Chromosome.
DR   AbasyAtlas; P54572; -.
DR   GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; EXP:UniProtKB.
DR   GO; GO:0004473; F:malate dehydrogenase (decarboxylating) (NADP+) activity; IBA:GO_Central.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0008948; F:oxaloacetate decarboxylase activity; EXP:UniProtKB.
DR   Gene3D; 3.40.50.10380; Malic enzyme, N-terminal domain; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR002912; ACT_dom.
DR   InterPro; IPR046346; Aminoacid_DH-like_N_sf.
DR   InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR   InterPro; IPR051674; Malate_Decarboxylase.
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   PANTHER; PTHR43237; NADP-DEPENDENT MALIC ENZYME; 1.
DR   PANTHER; PTHR43237:SF4; NADP-DEPENDENT MALIC ENZYME; 1.
DR   Pfam; PF02826; 2-Hacid_dh_C; 1.
DR   Pfam; PF00390; malic; 1.
DR   Pfam; PF03949; Malic_M; 1.
DR   PIRSF; PIRSF000106; ME; 1.
DR   SMART; SM01274; malic; 1.
DR   SMART; SM00919; Malic_M; 1.
DR   SUPFAM; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS51671; ACT; 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..439
FT                   /note="NAD-dependent malic enzyme 1"
FT                   /id="PRO_0000160208"
FT   DOMAIN          9..84
FT                   /note="ACT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT   ACT_SITE        112
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   ACT_SITE        167
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         209
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         210
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         235
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         268..271
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         347
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         373
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
SQ   SEQUENCE   439 AA;  45890 MW;  2C6863E83CA86939 CRC64;
     MIAKHMIRTL MIETPSVPGN LGRVATAIGL LGGDIGEVET VKVGPNYTMR NITVQVENEE
     QLQEVIAAVQ ALGEGIRLHT VSDEVLSAHE GGKIQMKSKM PIRSLAELGR VYTPGVADVC
     RLIEKEPEKA SIYTTISNSV AIVTDGTAIL GLGNIGSVAG MPVMEGKAAL FDQLAGISGI
     PILLDTSDPE EIIKTVKHIS PGFSGILLED IGSPHCFEIE DRLKEELNIP VMHDDQHGTA
     VVTLAAAISA CRSAGVDLKE AKVGQIGLGA AGVAICRMFM AYGVNAVYGT DKSESAMNRL
     EQYGGQAVSS IEELMETCDI VIATTGVPGL IKPAFVRSGQ VILALSNPKP EIEPEAALQA
     GAAYAADGRS VNNVLGFPGI FRGALNAKST EINHDMLVAA AEAIAACTKQ GDVVPQPLDS
     KVHHAVAAAV EHAALTAVK
//