HICDH_PYRHO
ID HICDH_PYRHO Reviewed; 345 AA.
AC O59394;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Isocitrate/homoisocitrate dehydrogenase {ECO:0000303|PubMed:15845397};
DE Short=HICDH;
DE EC=1.1.1.286;
DE AltName: Full=Beta-decarboxylating dehydrogenase;
GN OrderedLocusNames=PH1722;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBSTRATE SPECIFICITY.
RX PubMed=15845397; DOI=10.1016/j.bbrc.2005.03.169;
RA Miyazaki K.;
RT "Bifunctional isocitrate-homoisocitrate dehydrogenase: a missing link in
RT the evolution of beta-decarboxylating dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 331:341-346(2005).
CC -!- FUNCTION: Catalyzes the NAD(+)-dependent oxidative decarboxylation of
CC homoisocitrate to 2-oxoadipate (alpha-ketoadipate), and of isocitrate
CC to 2-oxoglutarate, at near equal efficiency. May thus play a dual role
CC in glutamate and lysine biosynthesis in vivo. Preferentially uses NAD
CC over NADP. {ECO:0000269|PubMed:15845397}.
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:0000269|PubMed:15845397};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23633;
CC Evidence={ECO:0000305|PubMed:15845397};
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:15845397};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11901;
CC Evidence={ECO:0000305|PubMed:15845397};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15845397};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q72IW9};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.4 uM for isocitrate (at 70 degrees Celsius and pH 7.8)
CC {ECO:0000269|PubMed:15845397};
CC KM=18.3 uM for homoisocitrate (at 70 degrees Celsius and pH 7.8)
CC {ECO:0000269|PubMed:15845397};
CC KM=77.1 uM for NAD (at 70 degrees Celsius and pH 7.8)
CC {ECO:0000269|PubMed:15845397};
CC Note=kcat is 14.8 sec(-1) with isocitrate as substrate and 13.7 sec(-
CC 1) with homoisocitrate as substrate.;
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 4/5.
CC {ECO:0000305|PubMed:15845397}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA30836.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BA000001; BAA30836.1; ALT_INIT; Genomic_DNA.
DR PIR; E71180; E71180.
DR RefSeq; WP_010885787.1; NC_000961.1.
DR AlphaFoldDB; O59394; -.
DR SMR; O59394; -.
DR STRING; 70601.3258153; -.
DR EnsemblBacteria; BAA30836; BAA30836; BAA30836.
DR GeneID; 1442568; -.
DR KEGG; pho:PH1722; -.
DR eggNOG; arCOG01163; Archaea.
DR OrthoDB; 33452at2157; -.
DR UniPathway; UPA00033; UER00030.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:InterPro.
DR GO; GO:0047046; F:homoisocitrate dehydrogenase activity; IEA:RHEA.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0033708; F:isocitrate-homoisocitrate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:InterPro.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniPathway.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR011828; LEU3_arc.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR02088; LEU3_arch; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW Magnesium; Manganese; Metal-binding; NAD; Oxidoreductase.
FT CHAIN 1..345
FT /note="Isocitrate/homoisocitrate dehydrogenase"
FT /id="PRO_0000418409"
FT BINDING 69..71
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 86
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 96
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 111
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 163
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 165
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 165
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 194
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 218
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 222
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 251..255
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 263
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
SQ SEQUENCE 345 AA; 38735 MW; AFA511F94CE1939D CRC64;
MYKVAVIKGD GIGPEVIDAA IRVVKSVTDK IKFYEFEGGL SVFKKYGVPI REEDLEEIRK
MDAILFGATT TPFDVPRYKS LIITLRKELD LYANLRIIPN FKLRKEIIIV RENSEGLYSG
EGAYDSNKVV DFRIITRKGA ERIAKFAVKL AKDRSTFLTF VHKANILESD RFFRKIVLDI
ARKEDVKVRE EIVDSFTIKL VKDPWNLGII LSENMFGDIL SDLATIHAGS IGIVPSGNYG
EDIALFEPIH GSAPDIAGKG IANPIGAILS AAMMLDYLGL DGSIIWKAVG RYVRRGNLTP
DMEGRATTLE VTNGIISEIY RLDEYEIDEV WRDEVRLGRI LLEIS
