ID   MAO2_ECOLI              Reviewed;         759 AA.
AC   P76558; P78200; P78201;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=NADP-dependent malic enzyme;
DE            Short=NADP-ME;
DE            EC=1.1.1.40;
GN   Name=maeB; Synonyms=ypfF; OrderedLocusNames=b2463, JW2447;
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=9205837; DOI=10.1093/dnares/4.2.91;
RA   Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA   Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA   Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA   Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT   "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT   genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT   its sequence features.";
RL   DNA Res. 4:91-113(1997).
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   CHARACTERIZATION.
RC   STRAIN=W / ATCC 11105 / DSM 1900;
RX   PubMed=36376;
RA   Iwakura M., Hattori J., Arita Y., Tokushige M., Katsuki H.;
RT   "Studies on regulatory functions of malic enzymes. VI. Purification and
RT   molecular properties of NADP-linked malic enzyme from Escherichia coli W.";
RL   J. Biochem. 85:1355-1365(1979).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP   ACTIVITY REGULATION, AND DOMAIN STRUCTURE.
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   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX   PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA   Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA   Grishin N.V., Zhao Y.;
RT   "Lysine acetylation is a highly abundant and evolutionarily conserved
RT   modification in Escherichia coli.";
RL   Mol. Cell. Proteomics 8:215-225(2009).
RN   [7]
RP   FUNCTION AS A MALOACTIC ENZYME.
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:17557829). In vitro, shows malolactic enzyme activity in the
CC       presence of NADPH. However, it is unlikely that this activity is of
CC       relevance in E.coli, which produces little NADPH (PubMed:33824210).
CC       {ECO:0000269|PubMed:17557829, ECO:0000269|PubMed:33824210}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate + NADP(+) = CO2 + NADPH + pyruvate;
CC         Xref=Rhea:RHEA:18253, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.40;
CC         Evidence={ECO:0000269|PubMed:17557829};
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=1.1.1.40;
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: Inhibited by 4 mM Mg(2+) and acetyl-CoA,
CC       competitively inhibited by fumarate and oxaloacetate. Activated by
CC       glutamate and aspartate, glucose-6-phosphate, acetyl-phosphate and 2 mM
CC       KCl. {ECO:0000269|PubMed:17557829}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3.41 mM for L-malate {ECO:0000269|PubMed:17557829};
CC         KM=0.0415 mM for NADP {ECO:0000269|PubMed:17557829};
CC         KM=6.21 mM for pyruvate {ECO:0000269|PubMed:17557829};
CC       pH dependence:
CC         Optimum pH is 7.5 for L-malate. {ECO:0000269|PubMed:17557829};
CC   -!- SUBUNIT: Homooligomer, possibly an octamer.
CC   -!- DOMAIN: The-C-terminal phosphate acetyltransferase domain is
CC       responsible for oligomerization, and is responsible for inhibition by
CC       acetyl-CoA and activation by glutamate, aspartate, and glucose-6-
CC       phosphate as shown by its deletion. The isolated domain does not
CC       catalyze the interconversion of acetyl-CoA and acetyl-phosphate.
CC       {ECO:0000269|PubMed:17557829}.
CC   -!- MISCELLANEOUS: Cannot use NAD(+).
CC   -!- SIMILARITY: In the N-terminal section; belongs to the malic enzymes
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the phosphate
CC       acetyltransferase and butyryltransferase family. {ECO:0000305}.
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DR   EMBL; U00096; AAC75516.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA16337.2; -; Genomic_DNA.
DR   PIR; F65021; F65021.
DR   RefSeq; NP_416958.1; NC_000913.3.
DR   RefSeq; WP_000342644.1; NZ_LN832404.1.
DR   AlphaFoldDB; P76558; -.
DR   SMR; P76558; -.
DR   BioGRID; 4260925; 8.
DR   DIP; DIP-10141N; -.
DR   IntAct; P76558; 10.
DR   STRING; 511145.b2463; -.
DR   BindingDB; P76558; -.
DR   ChEMBL; CHEMBL1687685; -.
DR   iPTMnet; P76558; -.
DR   jPOST; P76558; -.
DR   PaxDb; 511145-b2463; -.
DR   EnsemblBacteria; AAC75516; AAC75516; b2463.
DR   GeneID; 946947; -.
DR   KEGG; ecj:JW2447; -.
DR   KEGG; eco:b2463; -.
DR   PATRIC; fig|1411691.4.peg.4277; -.
DR   EchoBASE; EB3945; -.
DR   eggNOG; COG0280; Bacteria.
DR   eggNOG; COG0281; Bacteria.
DR   InParanoid; P76558; -.
DR   OMA; RNYFAAM; -.
DR   OrthoDB; 9805787at2; -.
DR   PhylomeDB; P76558; -.
DR   BioCyc; EcoCyc:MALIC-NADP-MONOMER; -.
DR   BioCyc; MetaCyc:MALIC-NADP-MONOMER; -.
DR   BRENDA; 1.1.1.40; 2026.
DR   SABIO-RK; P76558; -.
DR   PRO; PR:P76558; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR   GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR   GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR   GO; GO:0004473; F:malate dehydrogenase (decarboxylating) (NADP+) activity; IDA:EcoCyc.
DR   GO; GO:0043883; F:malolactic enzyme activity; IDA:EcoCyc.
DR   GO; GO:0030145; F:manganese ion binding; IDA:EcoCyc.
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; IEA:InterPro.
DR   CDD; cd05311; NAD_bind_2_malic_enz; 1.
DR   Gene3D; 3.40.50.10950; -; 1.
DR   Gene3D; 3.40.50.10750; Isocitrate/Isopropylmalate dehydrogenase-like; 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   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; IPR045213; Malic_NAD-bd_bact_type.
DR   InterPro; IPR012188; ME_PTA.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR042113; P_AcTrfase_dom1.
DR   InterPro; IPR042112; P_AcTrfase_dom2.
DR   InterPro; IPR002505; PTA_PTB.
DR   PANTHER; PTHR43237; NADP-DEPENDENT MALIC ENZYME; 1.
DR   PANTHER; PTHR43237:SF4; NADP-DEPENDENT MALIC ENZYME; 1.
DR   Pfam; PF00390; malic; 1.
DR   Pfam; PF03949; Malic_M; 1.
DR   Pfam; PF01515; PTA_PTB; 1.
DR   PIRSF; PIRSF036684; ME_PTA; 1.
DR   SMART; SM01274; malic; 1.
DR   SMART; SM00919; Malic_M; 1.
DR   SUPFAM; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00331; MALIC_ENZYMES; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Magnesium; Manganese; Metal-binding; Multifunctional enzyme;
KW   NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..759
FT                   /note="NADP-dependent malic enzyme"
FT                   /id="PRO_0000160242"
FT   REGION          1..428
FT                   /note="Malic enzyme"
FT   REGION          429..759
FT                   /note="Phosphate acetyltransferase; required for
FT                   oligomerization, inhibition by acetyl-CoA and activation by
FT                   glutamate, aspartate, and glucose-6-phosphate"
FT   ACT_SITE        39
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   ACT_SITE        94
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         136
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         137
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         162
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         195..198
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         288
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   BINDING         320
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P40927"
FT   MOD_RES         56
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000269|PubMed:18723842"
SQ   SEQUENCE   759 AA;  82417 MW;  9A8B67D9635E25BA CRC64;
     MDDQLKQSAL DFHEFPVPGK IQVSPTKPLA TQRDLALAYS PGVAAPCLEI EKDPLKAYKY
     TARGNLVAVI SNGTAVLGLG NIGALAGKPV MEGKGVLFKK FAGIDVFDIE VDELDPDKFI
     EVVAALEPTF GGINLEDIKA PECFYIEQKL RERMNIPVFH DDQHGTAIIS TAAILNGLRV
     VEKNISDVRM VVSGAGAAAI ACMNLLVALG LQKHNIVVCD SKGVIYQGRE PNMAETKAAY
     AVVDDGKRTL DDVIEGADIF LGCSGPKVLT QEMVKKMARA PMILALANPE PEILPPLAKE
     VRPDAIICTG RSDYPNQVNN VLCFPFIFRG ALDVGATAIN EEMKLAAVRA IAELAHAEQS
     EVVASAYGDQ DLSFGPEYII PKPFDPRLIV KIAPAVAKAA MESGVATRPI ADFDVYIDKL
     TEFVYKTNLF MKPIFSQARK APKRVVLPEG EEARVLHATQ ELVTLGLAKP ILIGRPNVIE
     MRIQKLGLQI KAGVDFEIVN NESDPRFKEY WTEYFQIMKR RGVTQEQAQR ALISNPTVIG
     AIMVQRGEAD AMICGTVGDY HEHFSVVKNV FGYRDGVHTA GAMNALLLPS GNTFIADTYV
     NDEPDAEELA EITLMAAETV RRFGIEPRVA LLSHSNFGSS DCPSSSKMRQ ALELVRERAP
     ELMIDGEMHG DAALVEAIRN DRMPDSSLKG SANILVMPNM EAARISYNLL RVSSSEGVTV
     GPVLMGVAKP VHVLTPIASV RRIVNMVALA VVEAQTQPL
//