ILVC_DESOH
ID ILVC_DESOH Reviewed; 352 AA.
AC A8ZTR0;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Ketol-acid reductoisomerase (NAD(+)) {ECO:0000303|PubMed:25172159};
DE Short=KARI {ECO:0000303|PubMed:25172159};
DE EC=1.1.1.382 {ECO:0000269|PubMed:25172159};
DE AltName: Full=Acetohydroxy-acid isomeroreductase {ECO:0000305};
DE Short=AHIR {ECO:0000305};
DE AltName: Full=Alpha-keto-beta-hydroxylacyl reductoisomerase {ECO:0000305};
GN OrderedLocusNames=Dole_2039 {ECO:0000312|EMBL:ABW67843.1};
OS Desulfococcus oleovorans (strain DSM 6200 / JCM 39069 / Hxd3).
OC Bacteria; Proteobacteria; Deltaproteobacteria; Desulfobacterales;
OC Desulfosudaceae; Desulfosudis.
OX NCBI_TaxID=96561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 6200 / JCM 39069 / Hxd3;
RG US DOE Joint Genome Institute;
RA Copeland A., Lucas S., Lapidus A., Barry K., Glavina del Rio T., Dalin E.,
RA Tice H., Pitluck S., Kiss H., Brettin T., Bruce D., Detter J.C., Han C.,
RA Schmutz J., Larimer F., Land M., Hauser L., Kyrpides N., Kim E., Wawrik B.,
RA Richardson P.;
RT "Complete sequence of Desulfococcus oleovorans Hxd3.";
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25172159; DOI=10.1016/j.ymben.2014.08.003;
RA Brinkmann-Chen S., Cahn J.K., Arnold F.H.;
RT "Uncovering rare NADH-preferring ketol-acid reductoisomerases.";
RL Metab. Eng. 26:17-22(2014).
CC -!- FUNCTION: Involved in the biosynthesis of branched-chain amino acids
CC (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction
CC of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In
CC the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl
CC migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the
CC reductase reaction, this 2-ketoacid undergoes a metal-dependent
CC reduction by NADH to yield (R)-2,3-dihydroxy-isovalerate.
CC {ECO:0000269|PubMed:25172159}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate + NAD(+) = (2S)-2-
CC acetolactate + H(+) + NADH; Xref=Rhea:RHEA:30627, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:49072, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58476; EC=1.1.1.382;
CC Evidence={ECO:0000269|PubMed:25172159};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:D0WGK0};
CC Note=Binds 2 magnesium ions per subunit.
CC {ECO:0000250|UniProtKB:D0WGK0};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=32 uM for NADH (at pH 7 with S2AL as substrate)
CC {ECO:0000269|PubMed:25172159};
CC Note=kcat is 0.25 sec(-1) for reductoisomerase activity with NADH (at
CC pH 7 with S2AL as substrate). {ECO:0000269|PubMed:25172159};
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
CC isoleucine from 2-oxobutanoate: step 2/4. {ECO:0000305}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
CC pyruvate: step 2/4. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ketol-acid reductoisomerase family.
CC {ECO:0000305}.
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DR EMBL; CP000859; ABW67843.1; -; Genomic_DNA.
DR RefSeq; WP_012175455.1; NC_009943.1.
DR AlphaFoldDB; A8ZTR0; -.
DR SMR; A8ZTR0; -.
DR STRING; 96561.Dole_2039; -.
DR EnsemblBacteria; ABW67843; ABW67843; Dole_2039.
DR KEGG; dol:Dole_2039; -.
DR eggNOG; COG0059; Bacteria.
DR HOGENOM; CLU_033821_1_2_7; -.
DR OMA; RAMFSWL; -.
DR OrthoDB; 188901at2; -.
DR UniPathway; UPA00047; UER00056.
DR UniPathway; UPA00049; UER00060.
DR Proteomes; UP000008561; Chromosome.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004455; F:ketol-acid reductoisomerase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009099; P:valine biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1040.10; -; 3.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR013023; KARI.
DR InterPro; IPR000506; KARI_C.
DR InterPro; IPR013116; KARI_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR21371; PTHR21371; 1.
DR Pfam; PF01450; IlvC; 1.
DR Pfam; PF07991; IlvN; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00465; ilvC; 1.
DR PROSITE; PS51851; KARI_C; 1.
DR PROSITE; PS51850; KARI_N; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Isomerase;
KW Magnesium; Metal-binding; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..352
FT /note="Ketol-acid reductoisomerase (NAD(+))"
FT /id="PRO_0000436832"
FT DOMAIN 11..199
FT /note="KARI N-terminal Rossmann"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01197"
FT DOMAIN 200..347
FT /note="KARI C-terminal knotted"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01198"
FT ACT_SITE 124
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 38..41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 100..103
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 153
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 208
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 208
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 212
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 244
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 248
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
FT BINDING 270
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:D0WGK0"
SQ SEQUENCE 352 AA; 38685 MW; 8EECF0979A02FF81 CRC64;
MPTINFGGVE ENVVTSEEFT LKKAREVLKN EVITVLGYGV QGPAQALNLK DNGFEVIIGQ
LEGDAYWEKA IADGFVPGKT LFPIEEAAKK GTIIKMLLSD AGQVAVWPKV KKCLKKGDAL
YFSHGFGIVY KDQTGIVPPK NVDVILVAPK GSGTNVRRNF KDGSGINSSY AVFQDATGRA
EERTIALGIA IGSGYLFPTT FEKEVFSDLT GERGVLMGCL AGTMEAQYNV LRKHGHSPSE
AFNETVEELT QSLIRLVAEN GMDWMFANCS TTAQRGALDW APKFRDAVAP VFDSLYRRVK
NGAETRRVLK VNSAPNYLEK LRKELDTIKN SEMWQAGAAV RALRPENRKK KK
