IDH_OSTTA
ID IDH_OSTTA Reviewed; 470 AA.
AC A0A096P8D3; A0A1Y5IEA9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 26-NOV-2014, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Isocitrate dehydrogenase (NAD(+)), mitochondrial {ECO:0000305};
DE Short=OtIDH {ECO:0000303|PubMed:25724193};
DE EC=1.1.1.41 {ECO:0000269|PubMed:25724193};
DE Flags: Precursor;
GN Name=IDH {ECO:0000303|PubMed:25724193};
GN OrderedLocusNames=Ot_13g02940 {ECO:0000312|EMBL:CEG00228.1};
GN ORFNames=BE221DRAFT_192402 {ECO:0000312|EMBL:OUS46403.1};
OS Ostreococcus tauri.
OC Eukaryota; Viridiplantae; Chlorophyta; Mamiellophyceae; Mamiellales;
OC Bathycoccaceae; Ostreococcus.
OX NCBI_TaxID=70448;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=OTTH0595;
RX PubMed=16868079; DOI=10.1073/pnas.0604795103;
RA Derelle E., Ferraz C., Rombauts S., Rouze P., Worden A.Z., Robbens S.,
RA Partensky F., Degroeve S., Echeynie S., Cooke R., Saeys Y., Wuyts J.,
RA Jabbari K., Bowler C., Panaud O., Piegu B., Ball S.G., Ral J.-P.,
RA Bouget F.-Y., Piganeau G., De Baets B., Picard A., Delseny M., Demaille J.,
RA Van de Peer Y., Moreau H.;
RT "Genome analysis of the smallest free-living eukaryote Ostreococcus tauri
RT unveils many unique features.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11647-11652(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RCC 1115;
RX PubMed=28695208; DOI=10.1126/sciadv.1700239;
RG DOE Joint Genome Institute;
RA Blanc-Mathieu R., Krasovec M., Hebrard M., Yau S., Desgranges E.,
RA Martin J., Schackwitz W., Kuo A., Salin G., Donnadieu C., Desdevises Y.,
RA Sanchez-Ferandin S., Moreau H., Rivals E., Grigoriev I.V., Grimsley N.,
RA Eyre-Walker A., Piganeau G.;
RT "Population genomics of picophytoplankton unveils novel chromosome
RT hypervariability.";
RL Sci. Adv. 3:e1700239-e1700239(2017).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF ASP-385 AND
RP MET-386.
RX PubMed=25724193; DOI=10.1096/fj.14-257014;
RA Tang W.G., Song P., Cao Z.Y., Wang P., Zhu G.P.;
RT "A unique homodimeric NAD+-linked isocitrate dehydrogenase from the
RT smallest autotrophic eukaryote Ostreococcus tauri.";
RL FASEB J. 29:2462-2472(2015).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 61-470 IN COMPLEX WITH
RP ISOCITRATE; NAD AND MAGNESIUM ION, AND SUBUNIT.
RA Zhu G.P., Tang W.G., Wang P.;
RT "Crystal structure of isocitrate dehydrogenase from Ostreococcus tauri.";
RL Submitted (DEC-2018) to the PDB data bank.
CC -!- FUNCTION: Performs an essential role in the oxidative function of the
CC tricarboxylic acid cycle and respiration (Probable). Catalyzes the
CC decarboxylation of isocitrate to produce 2-oxoglutarate and generate
CC NADH to provide electrons for energy production (Probable).
CC {ECO:0000305|PubMed:25724193}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH;
CC Xref=Rhea:RHEA:23632, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.41;
CC Evidence={ECO:0000269|PubMed:25724193};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23633;
CC Evidence={ECO:0000269|PubMed:25724193};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:25724193, ECO:0000269|Ref.4};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:25724193};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000269|Ref.4};
CC -!- ACTIVITY REGULATION: The homodimer exhibits allosteric regulation by
CC isocitrate. {ECO:0000269|PubMed:25724193}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=226 uM for NAD(+) with Mg(2+) as cofactor
CC {ECO:0000269|PubMed:25724193};
CC KM=265 uM for NAD(+) with Mn(2+) as cofactor
CC {ECO:0000269|PubMed:25724193};
CC pH dependence:
CC Optimum pH is 8.0 with Mn(2+) as cofactor and 8.5 with Mg(2+) as
CC cofactor. {ECO:0000269|PubMed:25724193};
CC Temperature dependence:
CC Optimum temperature is 45 degrees Celsius.
CC {ECO:0000269|PubMed:25724193};
CC -!- SUBUNIT: Forms homodimers. {ECO:0000269|PubMed:25724193}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; CAID01000013; CEG00228.1; -; Genomic_DNA.
DR EMBL; KZ155784; OUS46403.1; -; Genomic_DNA.
DR PDB; 6IXL; X-ray; 1.75 A; A/B/C/D=61-470.
DR PDB; 6IXN; X-ray; 1.87 A; A/B/C/D=61-470.
DR PDB; 6IXT; X-ray; 1.78 A; A/B/C/D=61-470.
DR PDB; 7E2W; X-ray; 1.80 A; A/B/C/D=61-470.
DR PDBsum; 6IXL; -.
DR PDBsum; 6IXN; -.
DR PDBsum; 6IXT; -.
DR PDBsum; 7E2W; -.
DR AlphaFoldDB; A0A096P8D3; -.
DR SMR; A0A096P8D3; -.
DR STRING; 70448.A0A096P8D3; -.
DR eggNOG; KOG1526; Eukaryota.
DR OrthoDB; 769322at2759; -.
DR Proteomes; UP000009170; Chromosome 13.
DR Proteomes; UP000195557; Unassembled WGS sequence.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006102; P:isocitrate metabolic process; IDA:UniProtKB.
DR GO; GO:0019674; P:NAD metabolic process; IDA:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IBA:GO_Central.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR InterPro; IPR004790; Isocitrate_DH_NADP.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR PANTHER; PTHR11822; PTHR11822; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Magnesium; Manganese; Metal-binding; Mitochondrion; NAD;
KW Oxidoreductase; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..470
FT /note="Isocitrate dehydrogenase (NAD(+)), mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000451874"
FT BINDING 138..140
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXN"
FT BINDING 157..163
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:7E2W"
FT BINDING 159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXN"
FT BINDING 193
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:7E2W"
FT BINDING 200
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:7E2W"
FT BINDING 275
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:7E2W"
FT BINDING 319
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:7E2W"
FT BINDING 319
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXT"
FT BINDING 324
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXN"
FT BINDING 343
FT /ligand="D-threo-isocitrate"
FT /ligand_id="ChEBI:CHEBI:15562"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:7E2W"
FT BINDING 343
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXT"
FT BINDING 347
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXT"
FT BINDING 380..385
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXN"
FT BINDING 399
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PDB:6IXN,
FT ECO:0007744|PDB:6IXT"
FT MUTAGEN 385
FT /note="D->R: Decreases affinity for NAD(+) 3-fold.
FT Decreases affinity for NAD(+) 78-fold; when associated with
FT H-386."
FT /evidence="ECO:0000269|PubMed:25724193"
FT MUTAGEN 386
FT /note="M->H: Decreases affinity for NAD(+) 78-fold; when
FT associated with R-385."
FT /evidence="ECO:0000269|PubMed:25724193"
FT CONFLICT 24
FT /note="A -> T (in Ref. 2; OUS46403)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="C -> S (in Ref. 2; OUS46403)"
FT /evidence="ECO:0000305"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 79..91
FT /evidence="ECO:0007829|PDB:6IXL"
FT TURN 92..96
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:6IXL"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 118..130
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 143..149
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 209..221
FT /evidence="ECO:0007829|PDB:6IXL"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 228..235
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 237..248
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 252..266
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 269..274
FT /evidence="ECO:0007829|PDB:6IXL"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 283..296
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 298..303
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 318..327
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 339..353
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 361..366
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:6IXL"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:6IXT"
FT HELIX 384..391
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 401..418
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 422..441
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 447..450
FT /evidence="ECO:0007829|PDB:6IXL"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:6IXN"
FT HELIX 457..467
FT /evidence="ECO:0007829|PDB:6IXL"
SQ SEQUENCE 470 AA; 52553 MW; 216B8DA0A13EB446 CRC64;
MTRVERGRVL ARAIERAVAH RASARRWTTT TRTPAWMVTG WMGGRGVDRS TAMTRFERCG
STASSKITAA PMVYVRGEEM TAYVMDLIRS RWIEPRVDVG GWETFDLRAK NRDDTEDRVL
RDVIEAGKRI KAIFKEPTVT PTADQVKRLG LRKSWGSPNG AMRRGWNGIT ISRDTIHIDG
VELGYKKPVL FERHAVGGEY SAGYKNVGKG KLTTTFTPSE GPDAGKTVVV DEREIVDEEA
AVVTYHNPYD NVHDLARFFF GRCLEAKVTP YVVTKKTVFK WQEPFWQIMR TVFDEEFKAQ
FVAAGVMKEG EELVHLLSDA ATMKLVQWRQ GGFGMAAHNY DGDVLTDELA QVHKSPGFIT
SNLVGVHEDG TLIKEFEASH GTVADMDEAR LRGEETSLNP LGMVEGLIGA MNHAADVHNI
DRDRTHAFTT KMRTVIHQLF REGKGTRDLC GPSGLTTEQF IDAVAERLDA
