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Ketol-acid reductoisomerase (NAD(P)( )) (KARI) (EC 1.1.1.383) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)

 ILVC_METS5              Reviewed;         335 AA.
A4YI15;
14-APR-2009, integrated into UniProtKB/Swiss-Prot.
29-MAY-2007, sequence version 1.
02-JUN-2021, entry version 88.
RecName: Full=Ketol-acid reductoisomerase (NAD(P)(+)) {ECO:0000303|PubMed:25172159};
Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
EC=1.1.1.383 {ECO:0000269|PubMed:25172159};
AltName: Full=Acetohydroxy-acid isomeroreductase {ECO:0000255|HAMAP-Rule:MF_00435};
Short=AHIR {ECO:0000255|HAMAP-Rule:MF_00435};
AltName: Full=Alpha-keto-beta-hydroxylacyl reductoisomerase {ECO:0000255|HAMAP-Rule:MF_00435};
AltName: Full=Ketol-acid reductoisomerase type 1 {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
AltName: Full=Ketol-acid reductoisomerase type I {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25172159};
Name=ilvC {ECO:0000255|HAMAP-Rule:MF_00435}; OrderedLocusNames=Msed_1927;
Metallosphaera sedula (strain ATCC 51363 / DSM 5348 / JCM 9185 / NBRC 15509
/ TH2).
Archaea; Crenarchaeota; Thermoprotei; Sulfolobales; Sulfolobaceae;
Metallosphaera.
NCBI_TaxID=399549;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=ATCC 51363 / DSM 5348 / JCM 9185 / NBRC 15509 / TH2;
PubMed=18083856; DOI=10.1128/aem.02019-07;
Auernik K.S., Maezato Y., Blum P.H., Kelly R.M.;
"The genome sequence of the metal-mobilizing, extremely thermoacidophilic
archaeon Metallosphaera sedula provides insights into bioleaching-
associated metabolism.";
Appl. Environ. Microbiol. 74:682-692(2008).
[2]
FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
SPECIFICITY.
PubMed=25172159; DOI=10.1016/j.ymben.2014.08.003;
Brinkmann-Chen S., Cahn J.K., Arnold F.H.;
"Uncovering rare NADH-preferring ketol-acid reductoisomerases.";
Metab. Eng. 26:17-22(2014).
-!- FUNCTION: Involved in the biosynthesis of branched-chain amino acids
(BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction
of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In
the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl
migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the
reductase reaction, this 2-ketoacid undergoes a metal-dependent
reduction by NADPH or NADH to yield (R)-2,3-dihydroxy-isovalerate.
{ECO:0000269|PubMed:25172159}.
-!- CATALYTIC ACTIVITY:
Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate + NAD(+) = (2S)-2-
acetolactate + H(+) + NADH; Xref=Rhea:RHEA:30627, ChEBI:CHEBI:15378,
ChEBI:CHEBI:49072, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
ChEBI:CHEBI:58476; EC=1.1.1.383;
Evidence={ECO:0000269|PubMed:25172159};
-!- CATALYTIC ACTIVITY:
Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (2S)-2-
acetolactate + H(+) + NADPH; Xref=Rhea:RHEA:22068, ChEBI:CHEBI:15378,
ChEBI:CHEBI:49072, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
ChEBI:CHEBI:58476; EC=1.1.1.383;
Evidence={ECO:0000269|PubMed:25172159};
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Evidence={ECO:0000255|HAMAP-Rule:MF_00435};
Note=Binds 2 magnesium ions per subunit. {ECO:0000255|HAMAP-
Rule:MF_00435};
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=24 uM for NADH (at pH 7 with S2AL as substrate)
{ECO:0000269|PubMed:25172159};
KM=31 uM for NADPH (at pH 7 with S2AL as substrate)
{ECO:0000269|PubMed:25172159};
Note=Kcat is 0.07 sec(-1) for reductoisomerase activity with NADPH
(at pH 7 with S2AL as substrate). Kcat is 0.06 sec(-1) for
reductoisomerase activity with NADH (at pH 7 with S2AL as substrate).
{ECO:0000269|PubMed:25172159};
-!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
isoleucine from 2-oxobutanoate: step 2/4. {ECO:0000255|HAMAP-
Rule:MF_00435}.
-!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
pyruvate: step 2/4. {ECO:0000255|HAMAP-Rule:MF_00435}.
-!- SIMILARITY: Belongs to the ketol-acid reductoisomerase family.
{ECO:0000255|HAMAP-Rule:MF_00435}.
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EMBL; CP000682; ABP96067.1; -; Genomic_DNA.
SMR; A4YI15; -.
STRING; 399549.Msed_1927; -.
EnsemblBacteria; ABP96067; ABP96067; Msed_1927.
KEGG; mse:Msed_1927; -.
eggNOG; arCOG04465; Archaea.
HOGENOM; CLU_033821_0_1_2; -.
OMA; RAMFSWL; -.
UniPathway; UPA00047; UER00056.
UniPathway; UPA00049; UER00060.
Proteomes; UP000000242; Chromosome.
GO; GO:0004455; F:ketol-acid reductoisomerase activity; IEA:UniProtKB-UniRule.
GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniRule.
GO; GO:0009099; P:valine biosynthetic process; IEA:UniProtKB-UniRule.
HAMAP; MF_00435; IlvC; 1.
InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
InterPro; IPR013023; KARI.
InterPro; IPR000506; KARI_C.
InterPro; IPR013116; KARI_N.
InterPro; IPR036291; NAD(P)-bd_dom_sf.
PANTHER; PTHR21371; PTHR21371; 1.
Pfam; PF01450; IlvC; 1.
Pfam; PF07991; IlvN; 1.
SUPFAM; SSF48179; SSF48179; 1.
SUPFAM; SSF51735; SSF51735; 1.
TIGRFAMs; TIGR00465; ilvC; 1.
PROSITE; PS51851; KARI_C; 1.
PROSITE; PS51850; KARI_N; 1.
1: Evidence at protein level;
Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Magnesium;
Metal-binding; NADP; Oxidoreductase; Reference proteome.
CHAIN 1..335
/note="Ketol-acid reductoisomerase (NAD(P)(+))"
/id="PRO_1000124312"
DOMAIN 5..185
/note="KARI N-terminal Rossmann"
/evidence="ECO:0000255|PROSITE-ProRule:PRU01197"
DOMAIN 186..331
/note="KARI C-terminal knotted"
/evidence="ECO:0000255|PROSITE-ProRule:PRU01198"
NP_BIND 28..31
/note="NADP"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
NP_BIND 86..89
/note="NADP"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
REGION 301..335
/note="Disordered"
/evidence="ECO:0000256|SAM:MobiDB-lite"
COMPBIAS 310..335
/note="Basic and acidic residues"
/evidence="ECO:0000256|SAM:MobiDB-lite"
ACT_SITE 111
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
METAL 194
/note="Magnesium 1"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
METAL 194
/note="Magnesium 2"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
METAL 198
/note="Magnesium 1"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
METAL 230
/note="Magnesium 2"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
METAL 234
/note="Magnesium 2"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
BINDING 52
/note="NADP"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
BINDING 56
/note="NADP"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
BINDING 137
/note="NADP; via amide nitrogen"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
BINDING 255
/note="Substrate"
/evidence="ECO:0000255|HAMAP-Rule:MF_00435"
SEQUENCE 335 AA; 37293 MW; 10A165E9EEB411B9 CRC64;
MSHIAKIYTD KDTTLDPMKG KKIAVLGYGS QGRAWALNLR DSGLQVTVGL EREGKSWEQA
KADGFTPKKT EDAVKDADVV IFLVPDMAQR LVYRERVQPY LREGMDLVFA HGFNIHYRLI
EPPSNVDVYM VAPKGPGPIV RDFYVKGGGV PVLVAVHQNH SGKALEKALA IAKALGGTRA
GAIETTFKEE TETDLIGEQT ILVGGVMELM KAAFETLVEM GYQPEVAYFE TINELKMIVD
LIYDKGFMGM LRAVSDTAKY GGFTVGKQVI NEETRRRLRE AAEKVRSGKF AEEWIEEYGR
GSPTLSKGLE EMDKSLEEQT GRRLKEIIER GRPKS


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Related Genes :
[ilvC Igag_1561] Ketol-acid reductoisomerase (NAD(P)(+)) (KARI) (EC 1.1.1.383) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)
[ilvC HY04AAS1_0065] Ketol-acid reductoisomerase (NAD(P)(+)) (KARI) (EC 1.1.1.383) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)
[ilvC Msed_1927] Ketol-acid reductoisomerase (NAD(P)(+)) (KARI) (EC 1.1.1.383) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)
[ilvC AF_1985] Ketol-acid reductoisomerase (NAD(P)(+)) (KARI) (EC 1.1.1.383) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)
[ilvC Swol_2144] Ketol-acid reductoisomerase (NAD(P)(+)) (KARI) (EC 1.1.1.383) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)
[ilv-2 B11H24.150 NCU03608] Ketol-acid reductoisomerase, mitochondrial (EC 1.1.1.86) (Acetohydroxy-acid reductoisomerase) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC MSMEG_2374 MSMEI_2314] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase) (Ketol-acid reductoisomerase type 1) (Ketol-acid reductoisomerase type I)
[ilvC A9R57_23920 ACU57_15125 AM464_12145 AUQ13_19615 BANRA_02438 BANRA_03179 BHS87_21145 BJJ90_26290 BMA87_16550 BMT91_24110 BUE81_11110 BvCms2454_00250 BvCmsHHP001_03804 BvCmsHHP056_00895 BvCmsKSP026_03770 BvCmsSINP011_03720 C5F72_26900 C5F73_26265 C5N07_17525 C9E25_10150 CA593_07130 CI694_09140 D0X26_19545 D3821_18110 D3Y67_15330 D9C99_19080 D9D44_19665 D9G69_18875 D9J52_16265 D9Z28_00985 DAH37_17760 DJ503_12515 DNC98_16435 DT034_15795 DTL43_17495 E2119_13480 E2127_09890 E2128_11645 E2129_09545 E2134_18980 E2135_06740 E4K51_16650 E4K53_17005 E4K55_16470 E5P28_18585 EA213_15335 EAI52_13870 EC3234A_70c00140 ECTO6_04741 EEP23_10785 EG808_18930 EI021_17430 EI032_19640 EI041_17065 EPT01_17940 ERS150873_02220 ETECE1441_04755 ETECE1649_04610 ETECE925_04728 EXX71_20460 EYD11_22900 EYV18_14040 FKC84_12005 FORC82_4764 FRV13_17280 FV293_16825 FWK02_04780 G5632_12230 G5688_10955 G9P50_21120 GHD50_17025 GKF86_12380 GKF89_18100 GQE33_16740 GQE64_18605 GQE67_14060 GQM17_18140 GRW02_18275 GRW05_20620 GRW80_15650 GRW81_20040 H4P50_25735 H4P51_25580 HH707_003176 HLT96_08360 HLU13_11580 HMQ05_13355 HNN86_14145 HNV44_14720 HPE39_00090 HV005_21285 HVV53_16590 HVX22_23140 HVX24_22470 HVY77_25445 HVY79_23550 HVY93_23410 HVZ24_22365 HVZ33_24300 HX136_24685 NCTC11022_04020 NCTC8500_05608 NCTC9045_05816 NCTC9062_03181 NCTC9117_06245 PGD_00196 RK56_018505 SAMEA3472047_02733 SAMEA3472080_05234 SAMEA3484427_04014 SAMEA3484429_03917 SAMEA3752559_04201 SAMEA3753300_03837 SK85_04104 WP2S18E08_47580 WP4S18E08_45240 WP7S17E04_43520] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC OR1_03722] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC ilvC_1 BACERE00184_03349 BLD50_14085 BLX06_04205 CN553_03290 CN950_30535 CN980_29805 COI98_10215 E2F98_04105 F8165_13500 FC692_14850 GE376_06985 HLB41_20130 WR51_07300] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC A3L25_026365 AYO08_28550 B7H18_09350 CBL13_04079 CBP06_22445 E4195_25690 E6B08_04450 EFJ98_14535 EQ845_21005 GN299_19190 H0H12_03745 HB4184_25300 ID616_25695 KF715C_ch50700 PPTS312_47750] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC D5R97_08635] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP1_0581] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC OR37_03918] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC OR214_02420] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC OR16_05297] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC A9485_01070 BLD50_04885 BLX06_01145 C1N66_00755 C2I25_02410 C6A78_15495 CN553_22610 CN602_08060 CN950_01030 CN980_07225 COI69_14165 COI98_01570 COJ13_19755 CSW12_18645 FORC47_1681 HLB41_18205] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC D5R99_05190] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC ACTI_11350] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC SAMN04487830_11772] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC GY22_13950] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC EAO72_34540] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP23_0753] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP2_0440] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP41_0495] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP30_0995] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP16_0320] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP25_0643] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP74_1036] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)
[ilvC HPHPP15_0712] Ketol-acid reductoisomerase (NADP(+)) (KARI) (EC 1.1.1.86) (Acetohydroxy-acid isomeroreductase) (AHIR) (Alpha-keto-beta-hydroxylacyl reductoisomerase)

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