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-NOV-2024, entry version 190.
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(+) = pyruvate + CO2 + NADPH;
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=oxaloacetate + H(+) = pyruvate + CO2; Xref=Rhea:RHEA:15641,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16526; EC=1.1.1.40;
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 PDB; 8JZO; EM; 2.86 A; A/B/C/D/E/F=1-759.
DR PDBsum; 8JZO; -.
DR AlphaFoldDB; P76558; -.
DR EMDB; EMD-36749; -.
DR SMR; P76558; -.
DR BioGRID; 4260925; 12.
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 KEGG; ecoc:C3026_13665; -.
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 FunFam; 3.40.50.10380:FF:000003; NADP-dependent malic enzyme; 1.
DR FunFam; 3.40.50.10750:FF:000002; NADP-dependent malic enzyme; 1.
DR FunFam; 3.40.50.10950:FF:000002; NADP-dependent malic enzyme; 1.
DR FunFam; 3.40.50.720:FF:000095; NADP-dependent malic enzyme; 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; 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; 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 3D-structure; Acetylation; Magnesium; Manganese; Metal-binding;
KW Multifunctional enzyme; 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
//
