ID   MAO1_ECOLI              Reviewed;         565 AA.
AC   P26616; P78224;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   06-DEC-2005, sequence version 4.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=NAD-dependent malic enzyme;
DE            Short=NAD-ME;
DE            EC=1.1.1.38;
GN   Name=maeA; Synonyms=sfcA; OrderedLocusNames=b1479, JW5238;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA   Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA   Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA   Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA   Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA   Wada C., Yamamoto Y., Horiuchi T.;
RT   "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT   the 28.0-40.1 min region on the linkage map.";
RL   DNA Res. 3:363-377(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-431.
RC   STRAIN=K12;
RX   PubMed=2199308; DOI=10.1093/genetics/125.2.261;
RA   Mahajan S.K., Chu C.C., Willis D.K., Templin A., Clark A.J.;
RT   "Physical analysis of spontaneous and mutagen-induced mutants of
RT   Escherichia coli K-12 expressing DNA exonuclease VIII activity.";
RL   Genetics 125:261-273(1990).
RN   [5]
RP   BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, ACTIVITY REGULATION, AND SUBUNIT.
RC   STRAIN=K12;
RX   PubMed=17557829; DOI=10.1128/jb.00428-07;
RA   Bologna F.P., Andreo C.S., Drincovich M.F.;
RT   "Escherichia coli malic enzymes: two isoforms with substantial differences
RT   in kinetic properties, metabolic regulation, and structure.";
RL   J. Bacteriol. 189:5937-5946(2007).
RN   [6]
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=17215140; DOI=10.1016/j.pep.2006.11.017;
RA   Wang J., Tan H., Zhao Z.K.;
RT   "Over-expression, purification, and characterization of recombinant NAD-
RT   malic enzyme from Escherichia coli K12.";
RL   Protein Expr. Purif. 53:97-103(2007).
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   -!- 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   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:17557829};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:17557829};
CC       Note=Divalent metal cations. Prefers magnesium or manganese.
CC       {ECO:0000269|PubMed:17557829};
CC   -!- ACTIVITY REGULATION: Non-competitively inhibited by high concentrations
CC       of NAD(+) and L-malate. Also inhibited by CoA, acetyl-phosphate,
CC       palmitoyl-CoA, and oxaloacetate. Activated by aspartate.
CC       {ECO:0000269|PubMed:17215140, ECO:0000269|PubMed:17557829}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.42 mM for L-malate {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC         KM=0.66 mM for L-malate {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC         KM=0.097 mM for NAD(+) {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC         KM=0.0688 mM for NAD(+) {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC         KM=2.59 mM for pyruvate {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC         Vmax=125.47 umol/min/mg enzyme {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC         Note=At pH 7.2.;
CC       pH dependence:
CC         Optimum pH is 7.2 to 7.5 for L-malate. {ECO:0000269|PubMed:17215140,
CC         ECO:0000269|PubMed:17557829};
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:17557829}.
CC   -!- MISCELLANEOUS: Can also use NADP(+) but is more effective with NAD(+).
CC   -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA39419.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAA39419.1; Type=Miscellaneous discrepancy; Note=The sequence differs from position 433 onward for unknown reasons.; Evidence={ECO:0000305};
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DR   EMBL; U00096; AAC74552.2; -; Genomic_DNA.
DR   EMBL; AP009048; BAA15127.2; -; Genomic_DNA.
DR   EMBL; X55956; CAA39419.1; ALT_SEQ; Genomic_DNA.
DR   PIR; B64901; B64901.
DR   RefSeq; NP_415996.2; NC_000913.3.
DR   RefSeq; WP_000433476.1; NZ_SSZK01000038.1.
DR   PDB; 6AGS; X-ray; 2.31 A; A=1-565.
DR   PDBsum; 6AGS; -.
DR   AlphaFoldDB; P26616; -.
DR   SMR; P26616; -.
DR   BioGRID; 4260208; 273.
DR   BioGRID; 850392; 3.
DR   IntAct; P26616; 3.
DR   STRING; 511145.b1479; -.
DR   ChEMBL; CHEMBL3286080; -.
DR   jPOST; P26616; -.
DR   PaxDb; 511145-b1479; -.
DR   EnsemblBacteria; AAC74552; AAC74552; b1479.
DR   GeneID; 946031; -.
DR   KEGG; ecj:JW5238; -.
DR   KEGG; eco:b1479; -.
DR   PATRIC; fig|1411691.4.peg.788; -.
DR   EchoBASE; EB0941; -.
DR   eggNOG; COG0281; Bacteria.
DR   HOGENOM; CLU_011405_5_2_6; -.
DR   InParanoid; P26616; -.
DR   OMA; QIVNHMV; -.
DR   OrthoDB; 3314528at2; -.
DR   PhylomeDB; P26616; -.
DR   BioCyc; EcoCyc:MALIC-NAD-MONOMER; -.
DR   BioCyc; MetaCyc:MALIC-NAD-MONOMER; -.
DR   BRENDA; 1.1.1.38; 2026.
DR   SABIO-RK; P26616; -.
DR   PRO; PR:P26616; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR   GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR   GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; IDA:EcoCyc.
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-UniRule.
DR   GO; GO:0006094; P:gluconeogenesis; IMP:EcoCyc.
DR   GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR   GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR   CDD; cd05312; NAD_bind_1_malic_enz; 1.
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   HAMAP; MF_01619; NAD_malic_enz; 1.
DR   InterPro; IPR046346; Aminoacid_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   InterPro; IPR023667; NAD_malic_enz_proteobac.
DR   PANTHER; PTHR23406; MALIC ENZYME-RELATED; 1.
DR   PANTHER; PTHR23406:SF32; NAD-DEPENDENT MALIC ENZYME, MITOCHONDRIAL; 1.
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; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00331; MALIC_ENZYMES; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Metal-binding; NAD; Oxidoreductase; Reference proteome.
FT   CHAIN           1..565
FT                   /note="NAD-dependent malic enzyme"
FT                   /id="PRO_0000160215"
FT   ACT_SITE        104
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        175
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         157
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         246
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250"
FT   BINDING         247
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250"
FT   BINDING         270
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250"
FT   BINDING         270
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         418
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            270
FT                   /note="Important for activity"
FT                   /evidence="ECO:0000250"
FT   STRAND          11..13
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           17..21
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            24..26
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           29..31
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           34..39
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           53..65
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           70..81
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           85..93
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           96..103
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           107..113
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           115..118
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          124..128
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           129..131
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           135..140
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          149..153
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            159..161
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           165..169
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           170..183
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           187..189
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          190..196
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           202..205
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           220..237
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          242..245
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           250..260
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            261..263
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          264..268
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            269..271
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           272..288
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          289..291
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            293..295
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          298..301
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           305..319
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            320..322
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           325..330
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          332..335
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          337..339
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           350..353
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           359..362
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           374..381
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          384..388
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           398..405
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          412..415
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           420..422
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           427..432
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   TURN            433..436
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          439..444
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          449..451
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          454..456
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           463..465
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           467..477
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           484..496
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           499..502
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          503..506
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           512..514
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           515..532
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   HELIX           541..550
FT                   /evidence="ECO:0007829|PDB:6AGS"
FT   STRAND          560..562
FT                   /evidence="ECO:0007829|PDB:6AGS"
SQ   SEQUENCE   565 AA;  63197 MW;  FFD61212F709EE3A CRC64;
     MEPKTKKQRS LYIPYAGPVL LEFPLLNKGS AFSMEERRNF NLLGLLPEVV ETIEEQAERA
     WIQYQGFKTE IDKHIYLRNI QDTNETLFYR LVNNHLDEMM PVIYTPTVGA ACERFSEIYR
     RSRGVFISYQ NRHNMDDILQ NVPNHNIKVI VVTDGERILG LGDQGIGGMG IPIGKLSLYT
     ACGGISPAYT LPVVLDVGTN NQQLLNDPLY MGWRNPRITD DEYYEFVDEF IQAVKQRWPD
     VLLQFEDFAQ KNAMPLLNRY RNEICSFNDD IQGTAAVTVG TLIAASRAAG GQLSEKKIVF
     LGAGSAGCGI AEMIISQTQR EGLSEEAARQ KVFMVDRFGL LTDKMPNLLP FQTKLVQKRE
     NLSDWDTDSD VLSLLDVVRN VKPDILIGVS GQTGLFTEEI IREMHKHCPR PIVMPLSNPT
     SRVEATPQDI IAWTEGNALV ATGSPFNPVV WKDKIYPIAQ CNNAFIFPGI GLGVIASGAS
     RITDEMLMSA SETLAQYSPL VLNGEGMVLP ELKDIQKVSR AIAFAVGKMA QQQGVAVKTS
     AEALQQAIDD NFWQAEYRDY RRTSI
//