AKSF_METJA
ID AKSF_METJA Reviewed; 347 AA.
AC Q58991; B1PL93;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Homoisocitrate dehydrogenase;
DE Short=HICDH;
DE EC=1.1.1.87 {ECO:0000269|PubMed:10940051, ECO:0000269|PubMed:18765671};
DE AltName: Full=Homo(2)-isocitrate/homo(3)-isocitrate dehydrogenase;
DE EC=1.1.1.- {ECO:0000269|PubMed:10940051, ECO:0000269|PubMed:18765671};
DE AltName: Full=Isohomocitrate dehydrogenase;
DE Short=IHDH;
DE AltName: Full=NAD-dependent threo-isohomocitrate dehydrogenase;
GN Name=aksF; Synonyms=icd; OrderedLocusNames=MJ1596;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=18765671; DOI=10.1074/jbc.m802159200;
RA Drevland R.M., Jia Y., Palmer D.R.J., Graham D.E.;
RT "Methanogen homoaconitase catalyzes both hydrolyase reactions in coenzyme B
RT biosynthesis.";
RL J. Biol. Chem. 283:28888-28896(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PATHWAY.
RX PubMed=10940051; DOI=10.1128/jb.182.17.5013-5016.2000;
RA Howell D.M., Graupner M., Xu H., White R.H.;
RT "Identification of enzymes homologous to isocitrate dehydrogenase that are
RT involved in coenzyme B and leucine biosynthesis in methanoarchaea.";
RL J. Bacteriol. 182:5013-5016(2000).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation and decarboxylation of
CC (2R,3S)-homoisocitrate, (2R,3S)-homo(2)-isocitrate and (2R,3S)-homo(3)-
CC isocitrate, into 2-oxoadipate, 2-oxopimelate (2-oxoheptanedioate), and
CC 2-oxosuberate, respectively. All these substrates are intermediates in
CC the biosynthesis of biotin and of 7-mercaptoheptanoate, a moiety of
CC coenzyme B in methanoarchaea (PubMed:18765671, PubMed:10940051). Is
CC also able to produce 2-oxoazelate from (2R,3S)-homo(4)-isocitrate in
CC vitro, but this substrate is probably not physiologically relevant
CC (PubMed:18765671). Is unable to use any isomer of isocitrate or
CC isopropylmalate as a substrate, and NADP as an oxidant
CC (PubMed:10940051). {ECO:0000269|PubMed:10940051,
CC ECO:0000269|PubMed:18765671}.
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; EC=1.1.1.87;
CC Evidence={ECO:0000269|PubMed:10940051, ECO:0000269|PubMed:18765671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11901;
CC Evidence={ECO:0000305|PubMed:10940051};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-iso(homo)2citrate + NAD(+) = 2-oxoheptanedioate + CO2
CC + NADH; Xref=Rhea:RHEA:68404, ChEBI:CHEBI:16526, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:72701, ChEBI:CHEBI:72722;
CC Evidence={ECO:0000269|PubMed:10940051, ECO:0000269|PubMed:18765671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68405;
CC Evidence={ECO:0000305|PubMed:10940051};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-iso(homo)3citrate + NAD(+) = 2-oxosuberate + CO2 +
CC NADH; Xref=Rhea:RHEA:68408, ChEBI:CHEBI:16526, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:177881, ChEBI:CHEBI:177882;
CC Evidence={ECO:0000269|PubMed:10940051, ECO:0000269|PubMed:18765671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68409;
CC Evidence={ECO:0000305|PubMed:10940051};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:10940051};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q72IW9};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.037 mM for (2R,3S)-homoisocitrate {ECO:0000269|PubMed:10940051};
CC KM=0.016 mM for (2R,3S)-homo(2)-isocitrate
CC {ECO:0000269|PubMed:10940051};
CC KM=0.021 mM for (2R,3S)-homo(3)-isocitrate
CC {ECO:0000269|PubMed:10940051};
CC Vmax=2.6 umol/min/mg enzyme with (2R,3S)-homoisocitrate as substrate
CC {ECO:0000269|PubMed:10940051};
CC Vmax=8.7 umol/min/mg enzyme with (2R,3S)-homo(2)-isocitrate as
CC substrate {ECO:0000269|PubMed:10940051};
CC Vmax=7.1 umol/min/mg enzyme with (2R,3S)-homo(3)-isocitrate as
CC substrate {ECO:0000269|PubMed:10940051};
CC Temperature dependence:
CC Stable at 100 degrees Celsius for 10 min.
CC {ECO:0000269|PubMed:10940051};
CC -!- PATHWAY: Organic acid metabolism; 2-oxosuberate biosynthesis.
CC {ECO:0000269|PubMed:10940051}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EU447775; ACA28837.1; -; Genomic_DNA.
DR EMBL; L77117; AAB99614.1; -; Genomic_DNA.
DR AlphaFoldDB; Q58991; -.
DR SMR; Q58991; -.
DR STRING; 243232.MJ_1596; -.
DR EnsemblBacteria; AAB99614; AAB99614; MJ_1596.
DR KEGG; mja:MJ_1596; -.
DR eggNOG; arCOG01163; Archaea.
DR HOGENOM; CLU_031953_0_1_2; -.
DR InParanoid; Q58991; -.
DR OMA; EYDLGAR; -.
DR PhylomeDB; Q58991; -.
DR BioCyc; MetaCyc:MON-2004; -.
DR BRENDA; 4.2.1.114; 3260.
DR UniPathway; UPA00919; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:InterPro.
DR GO; GO:0047046; F:homoisocitrate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0019298; P:coenzyme B biosynthetic process; IDA:MENGO.
DR GO; GO:0006102; P:isocitrate metabolic process; IBA:GO_Central.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:InterPro.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
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; Metal-binding; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..347
FT /note="Homoisocitrate dehydrogenase"
FT /id="PRO_0000083574"
FT BINDING 68..70
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 70
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 87
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 97
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 128
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 135
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 181
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 183
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 183
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 213
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 237
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 241
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 270..274
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT BINDING 282
FT /ligand="NADH"
FT /ligand_id="ChEBI:CHEBI:57945"
FT /evidence="ECO:0000250|UniProtKB:Q72IW9"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT CONFLICT 77
FT /note="K -> Q (in Ref. 2; AAB99614)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 347 AA; 38536 MW; 20D7BF9FDA451116 CRC64;
MMKVCVIEGD GIGKEVIPEA IKILNELGEF EIIKGEAGLE CLKKYGNALP EDTIEKAKEA
DIILFGAITS PKPGEVKNYK SPIITLRKMF HLYANVRPIN NFGIGQLIGK IADYEFLNAK
NIDIVIIREN TEDLYVGRER LENDTAIAER VITRKGSERI IRFAFEYAIK NNRKKVSCIH
KANVLRITDG LFLEVFNEIK KHYNIEADDY LVDSTAMNLI KHPEKFDVIV TTNMFGDILS
DEASALIGGL GLAPSANIGD DKALFEPVHG SAPDIAGKGI ANPMASILSI AMLFDYIGEK
EKGDLIREAV KYCLINKKVT PDLGGDLKTK DVGDEILNYI RKKLKGY
