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Protein

NAD-dependent malic enzyme, mitochondrial

Gene
N/A
Organism
Ascaris suum (Pig roundworm) (Ascaris lumbricoides)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

(S)-malate + NAD+ = pyruvate + CO2 + NADH.
Oxaloacetate = pyruvate + CO2.

Cofactori

Mg2+, Mn2+Note: Divalent metal cations. Prefers magnesium or manganese.

Enzyme regulationi

Subject to allosteric activation by fumarate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei78 – 781Allosteric activator
Binding sitei81 – 811Allosteric activator
Binding sitei105 – 1051Allosteric activator
Active sitei164 – 1641Proton donor
Active sitei237 – 2371Proton acceptor
Metal bindingi309 – 3091Divalent metal cation
Metal bindingi310 – 3101Divalent metal cation
Metal bindingi333 – 3331Divalent metal cationCurated
Binding sitei333 – 3331NAD2 Publications
Sitei333 – 3331Important for activity
Binding sitei472 – 4721NAD2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi219 – 2279NAD2 Publications
Nucleotide bindingi365 – 38218NAD2 PublicationsAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Metal-binding, NAD

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-18298.
BRENDAi1.1.1.38. 474.
SABIO-RKP27443.

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent malic enzyme, mitochondrial (EC:1.1.1.38)
Short name:
NAD-ME
OrganismiAscaris suum (Pig roundworm) (Ascaris lumbricoides)
Taxonomic identifieri6253 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaAscarididaAscaridoideaAscarididaeAscaris

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi96 – 961E → A: Reduces activity over 1000-fold. 1 Publication
Mutagenesisi164 – 1641Y → F: Reduces activity over 60000-fold. 1 Publication
Mutagenesisi216 – 2161D → A: Reduces activity over 50-fold. 1 Publication
Mutagenesisi237 – 2371K → A: Reduces activity over 100000-fold. 1 Publication
Mutagenesisi237 – 2371K → R: Reduces activity over 10-fold. 1 Publication
Mutagenesisi310 – 3101D → A: Reduces activity over 800-fold. 1 Publication
Mutagenesisi332 – 3321D → A: Reduces activity over 13000-fold. 1 Publication
Mutagenesisi333 – 3331D → A: Reduces activity over 100000-fold. 1 Publication
Mutagenesisi399 – 3991D → A: Reduces activity 10-fold. 1 Publication
Mutagenesisi478 – 4781E → A: Reduces activity over 1000-fold. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei‹1 – 38›38MitochondrionAdd
BLAST
Chaini39 – 643605NAD-dependent malic enzyme, mitochondrialPRO_0000018541Add
BLAST

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

Secondary structure

1
643
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi57 – 6610Combined sources
Helixi77 – 815Combined sources
Turni84 – 863Combined sources
Helixi89 – 913Combined sources
Helixi94 – 996Combined sources
Turni103 – 1053Combined sources
Helixi113 – 12614Combined sources
Beta strandi127 – 1293Combined sources
Helixi130 – 14314Combined sources
Helixi145 – 15410Combined sources
Helixi156 – 1638Combined sources
Helixi167 – 1759Combined sources
Beta strandi184 – 1885Combined sources
Helixi189 – 1913Combined sources
Helixi194 – 2018Combined sources
Beta strandi211 – 2155Combined sources
Beta strandi217 – 2204Combined sources
Turni221 – 2233Combined sources
Helixi227 – 2315Combined sources
Helixi232 – 24514Combined sources
Helixi249 – 2513Combined sources
Beta strandi252 – 2598Combined sources
Helixi264 – 2685Combined sources
Helixi283 – 30018Combined sources
Beta strandi305 – 3084Combined sources
Helixi313 – 32311Combined sources
Turni324 – 3263Combined sources
Beta strandi327 – 3315Combined sources
Helixi332 – 35221Combined sources
Helixi356 – 3583Combined sources
Beta strandi361 – 3644Combined sources
Helixi368 – 38215Combined sources
Turni383 – 3853Combined sources
Helixi388 – 3936Combined sources
Beta strandi395 – 3995Combined sources
Beta strandi405 – 4073Combined sources
Helixi413 – 4153Combined sources
Turni416 – 4183Combined sources
Beta strandi420 – 4223Combined sources
Helixi428 – 4358Combined sources
Beta strandi438 – 4425Combined sources
Helixi452 – 46110Combined sources
Beta strandi466 – 4694Combined sources
Helixi474 – 4763Combined sources
Helixi481 – 4866Combined sources
Turni487 – 4893Combined sources
Beta strandi493 – 4986Combined sources
Beta strandi503 – 5053Combined sources
Beta strandi508 – 5103Combined sources
Helixi517 – 5193Combined sources
Helixi521 – 53111Combined sources
Helixi538 – 55013Combined sources
Helixi554 – 5574Combined sources
Turni558 – 5603Combined sources
Helixi566 – 5683Combined sources
Helixi569 – 58618Combined sources
Beta strandi592 – 5943Combined sources
Helixi599 – 6068Combined sources
Helixi624 – 6274Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LLQX-ray2.30A/B39-643[»]
1O0SX-ray2.00A/B39-643[»]
ProteinModelPortaliP27443.
SMRiP27443. Positions 40-641.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27443.

Family & Domainsi

Sequence similaritiesi

Belongs to the malic enzymes family.Curated

Keywords - Domaini

Transit peptide

Family and domain databases

Gene3Di3.40.50.10380. 1 hit.
3.40.50.720. 1 hit.
InterProiIPR015884. Malic_enzyme_CS.
IPR012301. Malic_N_dom.
IPR012302. Malic_NAD-bd.
IPR001891. Malic_OxRdtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF00390. malic. 1 hit.
PF03949. Malic_M. 1 hit.
[Graphical view]
PIRSFiPIRSF000106. ME. 1 hit.
PRINTSiPR00072. MALOXRDTASE.
SMARTiSM01274. malic. 1 hit.
SM00919. Malic_M. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00331. MALIC_ENZYMES. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

P27443-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
PRVRSFIAHQ SGITSVIRRS PDIAHRMVRS LSVSSQRNKS VAHHEDVYSH
60 70 80 90 100
NLPPMDEKEM ALYKLYRPER VTPKKRSAEL LKEPRLNKGM GFSLYERQYL
110 120 130 140 150
GLHGLLPPAF MTQEQQAYRV ITKLREQPND LARYIQLDGL QDRNEKLFYR
160 170 180 190 200
VVCDHVKELM PIVYTPTVGL ACQNFGYIYR KPKGLYITIN DNSVSKIYQI
210 220 230 240 250
LSNWHEEDVR AIVVTDGERI LGLGDLGAYG IGIPVGKLAL YVALGGVQPK
260 270 280 290 300
WCLPVLLDVG TNNMDLLNDP FYIGLRHKRV RGKDYDTLLD NFMKACTKKY
310 320 330 340 350
GQKTLIQFED FANPNAFRLL DKYQDKYTMF NDDIQGTASV IVAGLLTCTR
360 370 380 390 400
VTKKLVSQEK YLFFGAGAAS TGIAEMIVHQ MQNEGISKEE ACNRIYLMDI
410 420 430 440 450
DGLVTKNRKE MNPRHVQFAK DMPETTSILE VIRAARPGAL IGASTVRGAF
460 470 480 490 500
NEEVIRAMAE INERPIIFAL SNPTSKAECT AEEAYTFTNG AALYASGSPF
510 520 530 540 550
PNFELNGHTY KPGQGNNAYI FPGVALGTIL FQIRHVDNDL FLLAAKKVAS
560 570 580 590 600
CVTEDSLKVG RVYPQLKEIR EISIQIAVEM AKYCYKNGTA NLYPQPEDLE
610 620 630 640
KYVRAQVYNT EYEELINATY DWPEQDMRHG FPVPVVRHDS MDG
Length:643
Mass (Da):72,757
Last modified:August 1, 1992 - v1
Checksum:i7B1A480F086FE267
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81055 mRNA. No translation available.
PIRiS29742.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81055 mRNA. No translation available.
PIRiS29742.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LLQX-ray2.30A/B39-643[»]
1O0SX-ray2.00A/B39-643[»]
ProteinModelPortaliP27443.
SMRiP27443. Positions 40-641.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-18298.
BRENDAi1.1.1.38. 474.
SABIO-RKP27443.

Miscellaneous databases

EvolutionaryTraceiP27443.

Family and domain databases

Gene3Di3.40.50.10380. 1 hit.
3.40.50.720. 1 hit.
InterProiIPR015884. Malic_enzyme_CS.
IPR012301. Malic_N_dom.
IPR012302. Malic_NAD-bd.
IPR001891. Malic_OxRdtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF00390. malic. 1 hit.
PF03949. Malic_M. 1 hit.
[Graphical view]
PIRSFiPIRSF000106. ME. 1 hit.
PRINTSiPR00072. MALOXRDTASE.
SMARTiSM01274. malic. 1 hit.
SM00919. Malic_M. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00331. MALIC_ENZYMES. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and nucleotide sequence of a full-length cDNA encoding Ascaris suum malic enzyme."
    Kulkarni G., Cook P.F., Harris B.G.
    Arch. Biochem. Biophys. 300:231-237(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Mapping the active site topography of the NAD-malic enzyme via alanine-scanning site-directed mutagenesis."
    Karsten W.E., Chooback L., Liu D., Hwang C.-C., Lynch C., Cook P.F.
    Biochemistry 38:10527-10532(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-96; ASP-216; ASP-310; ASP-332; ASP-333; ASP-399 AND GLU-478.
  3. "Lysine 199 is the general acid in the NAD-malic enzyme reaction."
    Liu D., Karsten W.E., Cook P.F.
    Biochemistry 39:11955-11960(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-164 AND LYS-237.
  4. "A catalytic triad is responsible for acid-base chemistry in the Ascaris suum NAD-malic enzyme."
    Karsten W.E., Liu D., Rao G.S., Harris B.G., Cook P.F.
    Biochemistry 44:3626-3635(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: MECHANISM, PH-DEPENDENCE OF ACTIVITY OF MUTANTS PHE-164; ARG-237 AND ALA-332.
  5. "Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 A resolution."
    Coleman D.E., Rao G.S.J., Goldsmith E.J., Cook P.F., Harris B.G.
    Biochemistry 41:6928-6938(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 39-643 IN COMPLEX WITH NAD.
  6. "Crystallographic studies on Ascaris suum NAD-malic enzyme bound to reduced cofactor and identification of an effector site."
    Rao G.S.J., Coleman D.E., Karsten W.E., Cook P.F., Harris B.G.
    J. Biol. Chem. 278:38051-38058(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 39-643 IN COMPLEX WITH NAD; MAGNESIUM AND INHIBITOR.

Entry informationi

Entry nameiMAOM_ASCSU
AccessioniPrimary (citable) accession number: P27443
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: May 11, 2016
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Miscellaneous

This isoenzyme can also use NADP+ but is more effective with NAD+.

Keywords - Technical termi

3D-structure, Allosteric enzyme

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.