ILVC_THEPS
ID ILVC_THEPS Reviewed; 332 AA.
AC K4LVZ1;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Ketol-acid reductoisomerase (NAD(+)) {ECO:0000303|PubMed:25172159};
DE Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
DE EC=1.1.1.382 {ECO:0000269|PubMed:25172159};
DE AltName: Full=Acetohydroxy-acid isomeroreductase {ECO:0000255|HAMAP-Rule:MF_00435};
DE Short=AHIR {ECO:0000255|HAMAP-Rule:MF_00435};
DE AltName: Full=Alpha-keto-beta-hydroxylacyl reductoisomerase {ECO:0000255|HAMAP-Rule:MF_00435};
DE AltName: Full=Ketol-acid reductoisomerase type 1 {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
DE AltName: Full=Ketol-acid reductoisomerase type I {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
GN Name=ilvC {ECO:0000255|HAMAP-Rule:MF_00435};
GN OrderedLocusNames=Tph_c19850 {ECO:0000312|EMBL:AFV12179.1};
OS Thermacetogenium phaeum (strain ATCC BAA-254 / DSM 26808 / PB).
OC Bacteria; Firmicutes; Clostridia; Thermoanaerobacterales;
OC Thermoanaerobacteraceae; Thermacetogenium.
OX NCBI_TaxID=1089553;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-254 / DSM 26808 / PB;
RX PubMed=23259483; DOI=10.1186/1471-2164-13-723;
RA Oehler D., Poehlein A., Leimbach A., Muller N., Daniel R., Gottschalk G.,
RA Schink B.;
RT "Genome-guided analysis of physiological and morphological traits of the
RT fermentative acetate oxidizer Thermacetogenium phaeum.";
RL BMC Genomics 13:723-723(2012).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
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:0000255|HAMAP-Rule:MF_00435};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_00435};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1 uM for NADH (at pH 7 with S2AL as substrate)
CC {ECO:0000269|PubMed:25172159};
CC KM=40 uM for NADPH (at pH 7 with S2AL as substrate)
CC {ECO:0000269|PubMed:25172159};
CC Note=kcat is 0.46 sec(-1) for reductoisomerase activity with NADH (at
CC pH 7 with S2AL as substrate). kcat is 0.25 sec(-1) for
CC reductoisomerase activity with NADPH (at pH 7 with S2AL as
CC substrate). {ECO:0000269|PubMed:25172159};
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
CC isoleucine from 2-oxobutanoate: step 2/4. {ECO:0000255|HAMAP-
CC Rule:MF_00435}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
CC pyruvate: step 2/4. {ECO:0000255|HAMAP-Rule:MF_00435}.
CC -!- SIMILARITY: Belongs to the ketol-acid reductoisomerase family.
CC {ECO:0000255|HAMAP-Rule:MF_00435}.
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DR EMBL; CP003732; AFV12179.1; -; Genomic_DNA.
DR RefSeq; WP_015051055.1; NZ_KI912609.1.
DR AlphaFoldDB; K4LVZ1; -.
DR SMR; K4LVZ1; -.
DR STRING; 1089553.Tph_c19850; -.
DR EnsemblBacteria; AFV12179; AFV12179; Tph_c19850.
DR KEGG; tpz:Tph_c19850; -.
DR eggNOG; COG0059; Bacteria.
DR HOGENOM; CLU_033821_0_1_9; -.
DR OMA; KGMDWMY; -.
DR OrthoDB; 188901at2; -.
DR UniPathway; UPA00047; UER00056.
DR UniPathway; UPA00049; UER00060.
DR Proteomes; UP000000467; Chromosome.
DR GO; GO:0004455; F:ketol-acid reductoisomerase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009099; P:valine biosynthetic process; IEA:UniProtKB-UniRule.
DR HAMAP; MF_00435; IlvC; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013023; KARI.
DR InterPro; IPR000506; KARI_C.
DR InterPro; IPR013116; KARI_N.
DR InterPro; IPR014359; KARI_prok.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR21371; PTHR21371; 1.
DR Pfam; PF01450; IlvC; 1.
DR Pfam; PF07991; IlvN; 1.
DR PIRSF; PIRSF000116; IlvC_gammaproteo; 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; Magnesium;
KW Metal-binding; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..332
FT /note="Ketol-acid reductoisomerase (NAD(+))"
FT /id="PRO_0000436835"
FT DOMAIN 1..181
FT /note="KARI N-terminal Rossmann"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01197"
FT DOMAIN 182..327
FT /note="KARI C-terminal knotted"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01198"
FT ACT_SITE 107
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 24..27
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 50
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 82..85
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 133
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 190
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 190
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 194
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 226
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 230
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 251
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
SQ SEQUENCE 332 AA; 36963 MW; D8343AABC818B66C CRC64;
MKIYYDQDAD LQYLDGKTVA VIGYGSQGHA QSQNLRDSGV KVVVADIPSS ENWKKAEEAQ
FQPLTADEAA READIIQILV PDEKQAALYR ESIAPNLRPG KALVFSHGFN IHFKQIVPPP
DVDVFMVAPK GPGHLVRRMY EEGAGVPSLV AVEQDYSGQA LNLALAYAKG IGATRAGVIQ
TTFKEETETD LFGEQAVLCG GITELIRAGF DTLVDAGYQP EIAYFECLHE MKLIVDLIYE
GGISTMRYSI SDTAEYGDLT RGKRIITEAT REEMKKILKE IQDGVFAREW LLENQVGRPV
YNALRRKEQN HLIETVGARL RGMMPWLKKK VI
