ID   A3DC45_ACET2            Unreviewed;       402 AA.
AC   A3DC45;
DT   20-MAR-2007, integrated into UniProtKB/TrEMBL.
DT   20-MAR-2007, sequence version 1.
DT   27-MAR-2024, entry version 111.
DE   RecName: Full=Isocitrate dehydrogenase [NADP] {ECO:0000256|PIRNR:PIRNR000108};
DE            EC=1.1.1.42 {ECO:0000256|PIRNR:PIRNR000108};
GN   OrderedLocusNames=Cthe_0285 {ECO:0000313|EMBL:ABN51524.1};
OS   Acetivibrio thermocellus (strain ATCC 27405 / DSM 1237 / JCM 9322 / NBRC
OS   103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) (Clostridium thermocellum).
OC   Bacteria; Bacillota; Clostridia; Eubacteriales; Oscillospiraceae;
OC   Acetivibrio.
OX   NCBI_TaxID=203119 {ECO:0000313|EMBL:ABN51524.1, ECO:0000313|Proteomes:UP000002145};
RN   [1] {ECO:0000313|Proteomes:UP000002145}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 /
RC   NRRL B-4536 / VPI 7372 {ECO:0000313|Proteomes:UP000002145};
RG   US DOE Joint Genome Institute;
RA   Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA   Glavina del Rio T., Hammon N., Israni S., Dalin E., Tice H., Pitluck S.,
RA   Chertkov O., Brettin T., Bruce D., Han C., Tapia R., Gilna P., Schmutz J.,
RA   Larimer F., Land M., Hauser L., Kyrpides N., Mikhailova N., Wu J.H.D.,
RA   Newcomb M., Richardson P.;
RT   "Complete sequence of Clostridium thermocellum ATCC 27405.";
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0007829|PDB:4AOU}
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH NADP.
RX   PubMed=23650595; DOI=10.1016/J.FOB.2012.06.003;
RA   Leiros H.K., Fedoy A.E., Leiros I., Steen I.H.;
RT   "The complex structures of isocitrate dehydrogenase from Clostridium
RT   thermocellum and Desulfotalea psychrophila suggest a new active site
RT   locking mechanism.";
RL   FEBS Open Bio 2:159-172(2012).
RN   [3] {ECO:0000313|EMBL:ABN51524.1, ECO:0000313|Proteomes:UP000002145}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 /
RC   NRRL B-4536 / VPI 7372 {ECO:0000313|Proteomes:UP000002145};
RX   PubMed=24295562; DOI=10.1186/1754-6834-6-179;
RA   Wilson C.M., Rodriguez M.Jr., Johnson C.M., Martin S.L., Chu T.M.,
RA   Wolfinger R.D., Hauser L.J., Land M.L., Klingeman D.M., Syed M.H.,
RA   Ragauskas A.J., Tschaplinski T.J., Mielenz J.R., Brown S.D.;
RT   "Global transcriptome analysis of Clostridium thermocellum ATCC 27405
RT   during growth on dilute acid pretreated Populus and switchgrass.";
RL   Biotechnol. Biofuels 6:179-179(2013).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC         Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC         Evidence={ECO:0000256|PIRNR:PIRNR000108};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|PIRNR:PIRNR000108,
CC         ECO:0000256|PIRSR:PIRSR000108-3};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000256|PIRNR:PIRNR000108,
CC         ECO:0000256|PIRSR:PIRSR000108-3};
CC       Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC       {ECO:0000256|PIRNR:PIRNR000108, ECO:0000256|PIRSR:PIRSR000108-3};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000256|ARBA:ARBA00001936};
CC   -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC       dehydrogenases family. {ECO:0000256|ARBA:ARBA00007769,
CC       ECO:0000256|PIRNR:PIRNR000108}.
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DR   EMBL; CP000568; ABN51524.1; -; Genomic_DNA.
DR   RefSeq; WP_003512448.1; NC_009012.1.
DR   PDB; 4AOU; X-ray; 2.50 A; A=1-402.
DR   PDBsum; 4AOU; -.
DR   AlphaFoldDB; A3DC45; -.
DR   SMR; A3DC45; -.
DR   STRING; 203119.Cthe_0285; -.
DR   GeneID; 57419390; -.
DR   KEGG; cth:Cthe_0285; -.
DR   eggNOG; COG0538; Bacteria.
DR   HOGENOM; CLU_023296_1_1_9; -.
DR   OrthoDB; 9765655at2; -.
DR   Proteomes; UP000002145; Chromosome.
DR   GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0006102; P:isocitrate metabolic process; IEA:InterPro.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
DR   InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR   InterPro; IPR004790; Isocitrate_DH_NADP.
DR   InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR   NCBIfam; TIGR00127; nadp_idh_euk; 1.
DR   PANTHER; PTHR11822:SF21; ISOCITRATE DEHYDROGENASE [NADP], MITOCHONDRIAL; 1.
DR   PANTHER; PTHR11822; NADP-SPECIFIC ISOCITRATE DEHYDROGENASE; 1.
DR   Pfam; PF00180; Iso_dh; 1.
DR   PIRSF; PIRSF000108; IDH_NADP; 1.
DR   SMART; SM01329; Iso_dh; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   PROSITE; PS00470; IDH_IMDH; 1.
PE   1: Evidence at protein level;
KW   3D-structure {ECO:0007829|PDB:4AOU};
KW   Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|PIRNR:PIRNR000108};
KW   Manganese {ECO:0000256|ARBA:ARBA00023211, ECO:0000256|PIRNR:PIRNR000108};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW   ECO:0000256|PIRNR:PIRNR000108};
KW   NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|PIRNR:PIRNR000108};
KW   Nucleotide-binding {ECO:0007829|PDB:4AOU};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW   ECO:0000256|PIRNR:PIRNR000108};
KW   Reference proteome {ECO:0000313|Proteomes:UP000002145};
KW   Tricarboxylic acid cycle {ECO:0000256|PIRNR:PIRNR000108}.
FT   DOMAIN          7..394
FT                   /note="Isopropylmalate dehydrogenase-like"
FT                   /evidence="ECO:0000259|SMART:SM01329"
FT   BINDING         75
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         77
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-2,
FT                   ECO:0007829|PDB:4AOU"
FT   BINDING         77
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         82
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         94..100
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-2"
FT   BINDING         94
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         96
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         100
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         109
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-2,
FT                   ECO:0007829|PDB:4AOU"
FT   BINDING         132
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-2,
FT                   ECO:0007829|PDB:4AOU"
FT   BINDING         139
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         210
FT                   /ligand="D-threo-isocitrate"
FT                   /ligand_id="ChEBI:CHEBI:15562"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         250
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         250
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-3"
FT   BINDING         255
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         273
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         273
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-3"
FT   BINDING         306
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         307
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         308
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         309
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         312
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         325
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   BINDING         372
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:4AOU"
FT   SITE            139
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-1"
FT   SITE            210
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000108-1"
SQ   SEQUENCE   402 AA;  45782 MW;  5A55781A7AC5B42E CRC64;
     MSKIKMKVPL VEMDGDEMTR IIWRLIKENL LEPYIELNTE YYDLGLENRD KTEDQVTIDA
     ARAIQKYGVG VKCATITPNA QRVEEYNLKK MWKSPNGTIR AILDGTVFRA PIVVNSIKPF
     VKGWKKPISI ARHAYGDVYK NVEYYVPSAG KAELVFTSEN GEVSRQTIHE FDGPGVIMGM
     HNTDKSIRSF ARACFNYALD MNQDLWFSTK DTISKTYDHR FKDIFQEIYE NEYKEKFEAK
     NLQYFYTLID DAVARIIRSE GGMVWACKNY DGDVMSDMVA SAFGSLAMMT SVLVSPDGKY
     EFEAAHGTVT RHYYKHLKGE ETSTNSMATI FAWTGALKKR GELDGIKELV DFATKLEQAS
     VQTIENGVMT KDLASLSEVP EKKIVNTEDF LKEIRKTFEG MA
//