HICDH_THET8
ID HICDH_THET8 Reviewed; 334 AA.
AC Q5SIJ1; Q8RQU4;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Isocitrate/homoisocitrate dehydrogenase {ECO:0000250|UniProtKB:Q72IW9};
DE EC=1.1.1.286 {ECO:0000250|UniProtKB:Q72IW9};
DE AltName: Full=Homoisocitrate dehydrogenase {ECO:0000303|PubMed:21813504};
DE Short=HICDH {ECO:0000303|PubMed:21813504};
GN Name=hicd; Synonyms=hdh; OrderedLocusNames=TTHA1378;
OS Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=300852;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Miyazaki K.;
RT "Homoisocitrate dehydrogenase from Thermus thermophilus HB8.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T.,
RA Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.;
RT "Complete genome sequence of Thermus thermophilus HB8.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH THE SYNTHETIC
RP INHIBITOR (2S,3S)-THIAHOMOISOCITRATE, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBUNIT, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RX PubMed=21813504; DOI=10.1093/jb/mvr097;
RA Nango E., Yamamoto T., Kumasaka T., Eguchi T.;
RT "Structure of Thermus thermophilus homoisocitrate dehydrogenase in complex
RT with a designed inhibitor.";
RL J. Biochem. 150:607-614(2011).
CC -!- FUNCTION: Catalyzes the NAD(+)-dependent oxidative decarboxylation of
CC homoisocitrate to 2-oxoadipate (alpha-ketoadipate), a reaction involved
CC in lysine biosynthesis through the alpha-aminoadipate pathway
CC (PubMed:21813504). In addition, has high activity with isocitrate, but
CC is inactive with 3-isopropylmalate (By similarity).
CC {ECO:0000250|UniProtKB:Q72IW9, ECO:0000269|PubMed:21813504}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-homoisocitrate + NAD(+) = 2-oxoadipate + CO2 + NADH;
CC Xref=Rhea:RHEA:11900, ChEBI:CHEBI:15404, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57499, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.286; Evidence={ECO:0000269|PubMed:21813504};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11901;
CC Evidence={ECO:0000305|PubMed:21813504};
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;
CC EC=1.1.1.286; Evidence={ECO:0000250|UniProtKB:Q72IW9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23633;
CC Evidence={ECO:0000250|UniProtKB:Q72IW9};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:21813504};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:21813504};
CC -!- ACTIVITY REGULATION: Competitively inhibited by (2S,3S)-
CC thiahomoisocitrate in vitro. {ECO:0000269|PubMed:21813504}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 4/5.
CC -!- SUBUNIT: Homotetramer. Dimer of dimers. The homotetramer can
CC transiently dissociate into homodimers. {ECO:0000269|PubMed:21813504}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; AB104528; BAD06517.1; -; Genomic_DNA.
DR EMBL; AP008226; BAD71201.1; -; Genomic_DNA.
DR RefSeq; WP_011173431.1; NC_006461.1.
DR RefSeq; YP_144644.1; NC_006461.1.
DR PDB; 3ASJ; X-ray; 2.60 A; A/B/C/D=1-334.
DR PDBsum; 3ASJ; -.
DR AlphaFoldDB; Q5SIJ1; -.
DR SMR; Q5SIJ1; -.
DR STRING; 300852.55772760; -.
DR EnsemblBacteria; BAD71201; BAD71201; BAD71201.
DR GeneID; 3169501; -.
DR KEGG; ttj:TTHA1378; -.
DR PATRIC; fig|300852.9.peg.1354; -.
DR eggNOG; COG0473; Bacteria.
DR HOGENOM; CLU_031953_0_1_0; -.
DR OMA; TCAHKAN; -.
DR PhylomeDB; Q5SIJ1; -.
DR BioCyc; MetaCyc:MON-6726; -.
DR BRENDA; 1.1.1.87; 2305.
DR UniPathway; UPA00033; UER00030.
DR Proteomes; UP000000532; Chromosome.
DR GO; GO:0047046; F:homoisocitrate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniPathway.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Lysine biosynthesis; Magnesium;
KW Metal-binding; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..334
FT /note="Isocitrate/homoisocitrate dehydrogenase"
FT /id="PRO_0000422303"
FT BINDING 70..72
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 72
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 85
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 88
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 98
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 118
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 125
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 171
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 173
FT /ligand="(2R,3S)-homoisocitrate"
FT /ligand_id="ChEBI:CHEBI:15404"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 173
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 204
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 228
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 232
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 261..265
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 273
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT SITE 85
FT /note="Important for substrate specificity and
FT discrimination against 3-isopropylmalate"
FT /evidence="ECO:0000250"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 14..27
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 41..45
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 53..60
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 135..143
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 144..159
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:3ASJ"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:3ASJ"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 179..189
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 197..202
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 203..212
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 224..236
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:3ASJ"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:3ASJ"
FT TURN 264..268
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 275..288
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 291..307
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3ASJ"
FT HELIX 320..331
FT /evidence="ECO:0007829|PDB:3ASJ"
SQ SEQUENCE 334 AA; 35922 MW; 82B018FED744FB49 CRC64;
MAYRICLIEG DGIGHEVIPA ARRVLEATGL PLEFVEAEAG WETFERRGTS VPEETVEKIL
SCHATLFGAA TSPTRKVPGF FGAIRYLRRR LDLYANVRPA KSRPVPGSRP GVDLVIVREN
TEGLYVEQER RYLDVAIADA VISKKASERI GRAALRIAEG RPRKTLHIAH KANVLPLTQG
LFLDTVKEVA KDFPLVNVQD IIVDNCAMQL VMRPERFDVI VTTNLLGDIL SDLAAGLVGG
LGLAPSGNIG DTTAVFEPVH GSAPDIAGKG IANPTAAILS AAMMLDYLGE KEAAKRVEKA
VDLVLERGPR TPDLGGDATT EAFTEAVVEA LKSL
