ILVC_SYNWW
ID ILVC_SYNWW Reviewed; 337 AA.
AC Q0AV19;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Ketol-acid reductoisomerase (NAD(P)(+)) {ECO:0000303|PubMed:25172159};
DE Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
DE EC=1.1.1.383 {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}; OrderedLocusNames=Swol_2144;
OS Syntrophomonas wolfei subsp. wolfei (strain DSM 2245B / Goettingen).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Syntrophomonadaceae;
OC Syntrophomonas.
OX NCBI_TaxID=335541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 2245B / Goettingen;
RX PubMed=21966920; DOI=10.1111/j.1462-2920.2010.02237.x;
RA Sieber J.R., Sims D.R., Han C., Kim E., Lykidis A., Lapidus A.L.,
RA McDonnald E., Rohlin L., Culley D.E., Gunsalus R., McInerney M.J.;
RT "The genome of Syntrophomonas wolfei: new insights into syntrophic
RT metabolism and biohydrogen production.";
RL Environ. Microbiol. 12:2289-2301(2010).
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 NADPH or 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=1.1.1.383;
CC Evidence={ECO:0000269|PubMed:25172159};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (2S)-2-
CC acetolactate + H(+) + NADPH; Xref=Rhea:RHEA:22068, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:49072, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58476; EC=1.1.1.383;
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=44 uM for NADPH (at pH 7 with S2AL as substrate)
CC {ECO:0000269|PubMed:25172159};
CC KM=57 uM for NADH (at pH 7 with S2AL as substrate)
CC {ECO:0000269|PubMed:25172159};
CC Note=kcat is 0.28 sec(-1) for reductoisomerase activity with NADH (at
CC pH 7 with S2AL as substrate). kcat is 0.22 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; CP000448; ABI69435.1; -; Genomic_DNA.
DR RefSeq; WP_011641526.1; NC_008346.1.
DR AlphaFoldDB; Q0AV19; -.
DR SMR; Q0AV19; -.
DR STRING; 335541.Swol_2144; -.
DR EnsemblBacteria; ABI69435; ABI69435; Swol_2144.
DR KEGG; swo:Swol_2144; -.
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; UP000001968; 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; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..337
FT /note="Ketol-acid reductoisomerase (NAD(P)(+))"
FT /id="PRO_1000050586"
FT DOMAIN 2..187
FT /note="KARI N-terminal Rossmann"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01197"
FT DOMAIN 188..333
FT /note="KARI C-terminal knotted"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01198"
FT ACT_SITE 113
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 25..28
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000305"
FT BINDING 48
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000305"
FT BINDING 88..91
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000305"
FT BINDING 139
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000305"
FT BINDING 196
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 196
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 232
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 236
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 257
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
SQ SEQUENCE 337 AA; 37043 MW; E46F1E5998933751 CRC64;
MARMFYDADA NLENLKGKTI AVMGFGSQGH AQAQNLKESG LNVIVGLRKP FDEASEKEWN
AVIAAGITPM SVAEAAEAAD VIQILLPDEV QARVYNAEIK PYLKAGNALG FSHGFNIHFG
QIVPPAFVDV FMVAPKSPGH LVRRMYVKGA GVPGLVAVQQ DYSGKAKDLA LAYACGIGCT
RAGVIETSFQ EETETDLFGE QCVLCGGVTE LVKAGFETLV EAGYQPEIAY FECMHELKLI
VDLMYEGGMS YMRYSISDTA EWGDYTKGPE IIGEEARYAM YEALQDIQDG SFAKGWLLEN
MVGRPRFNAL KRQNREHLIE EVGAELRGMM PWLKETK
