MAOM_ASCSU
ID MAOM_ASCSU Reviewed; 643 AA.
AC P27443;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=NAD-dependent malic enzyme, mitochondrial;
DE Short=NAD-ME;
DE EC=1.1.1.38;
DE Flags: Precursor; Fragment;
OS Ascaris suum (Pig roundworm) (Ascaris lumbricoides).
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Spirurina; Ascaridomorpha; Ascaridoidea; Ascarididae; Ascaris.
OX NCBI_TaxID=6253;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8424657; DOI=10.1006/abbi.1993.1032;
RA Kulkarni G., Cook P.F., Harris B.G.;
RT "Cloning and nucleotide sequence of a full-length cDNA encoding Ascaris
RT suum malic enzyme.";
RL Arch. Biochem. Biophys. 300:231-237(1993).
RN [2]
RP MUTAGENESIS OF GLU-96; ASP-216; ASP-310; ASP-332; ASP-333; ASP-399 AND
RP GLU-478.
RX PubMed=10441149; DOI=10.1021/bi9906165;
RA Karsten W.E., Chooback L., Liu D., Hwang C.-C., Lynch C., Cook P.F.;
RT "Mapping the active site topography of the NAD-malic enzyme via alanine-
RT scanning site-directed mutagenesis.";
RL Biochemistry 38:10527-10532(1999).
RN [3]
RP MUTAGENESIS OF TYR-164 AND LYS-237.
RX PubMed=11009609; DOI=10.1021/bi000790p;
RA Liu D., Karsten W.E., Cook P.F.;
RT "Lysine 199 is the general acid in the NAD-malic enzyme reaction.";
RL Biochemistry 39:11955-11960(2000).
RN [4]
RP MECHANISM, AND PH-DEPENDENCE OF ACTIVITY OF MUTANTS PHE-164; ARG-237 AND
RP ALA-332.
RX PubMed=15736972; DOI=10.1021/bi047826o;
RA Karsten W.E., Liu D., Rao G.S., Harris B.G., Cook P.F.;
RT "A catalytic triad is responsible for acid-base chemistry in the Ascaris
RT suum NAD-malic enzyme.";
RL Biochemistry 44:3626-3635(2005).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 39-643 IN COMPLEX WITH NAD.
RX PubMed=12033925; DOI=10.1021/bi0255120;
RA Coleman D.E., Rao G.S.J., Goldsmith E.J., Cook P.F., Harris B.G.;
RT "Crystal structure of the malic enzyme from Ascaris suum complexed with
RT nicotinamide adenine dinucleotide at 2.3 A resolution.";
RL Biochemistry 41:6928-6938(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 39-643 IN COMPLEX WITH NAD;
RP MAGNESIUM AND INHIBITOR.
RX PubMed=12853453; DOI=10.1074/jbc.m305145200;
RA Rao G.S.J., Coleman D.E., Karsten W.E., Cook P.F., Harris B.G.;
RT "Crystallographic studies on Ascaris suum NAD-malic enzyme bound to reduced
RT cofactor and identification of an effector site.";
RL J. Biol. Chem. 278:38051-38058(2003).
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 Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Note=Divalent metal cations. Prefers magnesium or manganese.;
CC -!- ACTIVITY REGULATION: Subject to allosteric activation by fumarate.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- MISCELLANEOUS: This isoenzyme can also use NADP(+) but is more
CC effective with NAD(+).
CC -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
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DR EMBL; M81055; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; S29742; S29742.
DR PDB; 1LLQ; X-ray; 2.30 A; A/B=39-643.
DR PDB; 1O0S; X-ray; 2.00 A; A/B=39-643.
DR PDBsum; 1LLQ; -.
DR PDBsum; 1O0S; -.
DR AlphaFoldDB; P27443; -.
DR SMR; P27443; -.
DR PRIDE; P27443; -.
DR BioCyc; MetaCyc:MON-18298; -.
DR BRENDA; 1.1.1.38; 474.
DR SABIO-RK; P27443; -.
DR EvolutionaryTrace; P27443; -.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; IEA:UniProtKB-EC.
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:0008152; P:metabolic process; IEA:UniProtKB-KW.
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 3D-structure; Allosteric enzyme; Metal-binding; Mitochondrion; NAD;
KW Oxidoreductase; Transit peptide.
FT TRANSIT <1..38
FT /note="Mitochondrion"
FT CHAIN 39..643
FT /note="NAD-dependent malic enzyme, mitochondrial"
FT /id="PRO_0000018541"
FT ACT_SITE 164
FT /note="Proton donor"
FT ACT_SITE 237
FT /note="Proton acceptor"
FT BINDING 116
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000305|PubMed:12853453"
FT BINDING 119
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000305|PubMed:12853453"
FT BINDING 143
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000305|PubMed:12853453"
FT BINDING 219..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12033925,
FT ECO:0000269|PubMed:12853453"
FT BINDING 309
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT BINDING 310
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT BINDING 333
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT BINDING 333
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12033925,
FT ECO:0000269|PubMed:12853453"
FT BINDING 365..382
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12033925,
FT ECO:0000269|PubMed:12853453"
FT BINDING 472
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12033925,
FT ECO:0000269|PubMed:12853453"
FT SITE 333
FT /note="Important for activity"
FT MUTAGEN 96
FT /note="E->A: Reduces activity over 1000-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT MUTAGEN 164
FT /note="Y->F: Reduces activity over 60000-fold."
FT /evidence="ECO:0000269|PubMed:11009609"
FT MUTAGEN 216
FT /note="D->A: Reduces activity over 50-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT MUTAGEN 237
FT /note="K->A: Reduces activity over 100000-fold."
FT /evidence="ECO:0000269|PubMed:11009609"
FT MUTAGEN 237
FT /note="K->R: Reduces activity over 10-fold."
FT /evidence="ECO:0000269|PubMed:11009609"
FT MUTAGEN 310
FT /note="D->A: Reduces activity over 800-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT MUTAGEN 332
FT /note="D->A: Reduces activity over 13000-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT MUTAGEN 333
FT /note="D->A: Reduces activity over 100000-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT MUTAGEN 399
FT /note="D->A: Reduces activity 10-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT MUTAGEN 478
FT /note="E->A: Reduces activity over 1000-fold."
FT /evidence="ECO:0000269|PubMed:10441149"
FT NON_TER 1
FT HELIX 57..66
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 94..99
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 113..126
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 130..143
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 145..154
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 156..163
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 167..175
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 194..201
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:1LLQ"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 227..231
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 232..245
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 252..259
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 264..268
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 283..300
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 313..323
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 332..352
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 368..382
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 383..385
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 388..393
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 395..399
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:1LLQ"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 416..418
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 420..422
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 428..435
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 438..442
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 452..461
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 466..469
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 474..476
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 481..486
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 493..498
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 517..519
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 521..531
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 538..550
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 554..557
FT /evidence="ECO:0007829|PDB:1O0S"
FT TURN 558..560
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 566..568
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 569..586
FT /evidence="ECO:0007829|PDB:1O0S"
FT STRAND 592..594
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 599..606
FT /evidence="ECO:0007829|PDB:1O0S"
FT HELIX 624..627
FT /evidence="ECO:0007829|PDB:1O0S"
SQ SEQUENCE 643 AA; 72757 MW; 7B1A480F086FE267 CRC64;
PRVRSFIAHQ SGITSVIRRS PDIAHRMVRS LSVSSQRNKS VAHHEDVYSH NLPPMDEKEM
ALYKLYRPER VTPKKRSAEL LKEPRLNKGM GFSLYERQYL GLHGLLPPAF MTQEQQAYRV
ITKLREQPND LARYIQLDGL QDRNEKLFYR VVCDHVKELM PIVYTPTVGL ACQNFGYIYR
KPKGLYITIN DNSVSKIYQI LSNWHEEDVR AIVVTDGERI LGLGDLGAYG IGIPVGKLAL
YVALGGVQPK WCLPVLLDVG TNNMDLLNDP FYIGLRHKRV RGKDYDTLLD NFMKACTKKY
GQKTLIQFED FANPNAFRLL DKYQDKYTMF NDDIQGTASV IVAGLLTCTR VTKKLVSQEK
YLFFGAGAAS TGIAEMIVHQ MQNEGISKEE ACNRIYLMDI DGLVTKNRKE MNPRHVQFAK
DMPETTSILE VIRAARPGAL IGASTVRGAF NEEVIRAMAE INERPIIFAL SNPTSKAECT
AEEAYTFTNG AALYASGSPF PNFELNGHTY KPGQGNNAYI FPGVALGTIL FQIRHVDNDL
FLLAAKKVAS CVTEDSLKVG RVYPQLKEIR EISIQIAVEM AKYCYKNGTA NLYPQPEDLE
KYVRAQVYNT EYEELINATY DWPEQDMRHG FPVPVVRHDS MDG
