ID ILVC_MYCBO Reviewed; 333 AA. AC P65150; A0A1R3Y2U9; O53248; X2BMA8; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2017, sequence version 3. DT 02-SEP-2026, entry version 123. DE RecName: Full=Ketol-acid reductoisomerase (NADP(+)) {ECO:0000255|HAMAP-Rule:MF_00435}; DE Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435}; DE EC=1.1.1.86 {ECO:0000255|HAMAP-Rule:MF_00435}; 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}; DE AltName: Full=Ketol-acid reductoisomerase type I {ECO:0000255|HAMAP-Rule:MF_00435}; GN Name=ilvC {ECO:0000255|HAMAP-Rule:MF_00435}; GN OrderedLocusNames=BQ2027_MB3026C; OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97). OC Bacteria; Bacillati; Actinomycetota; Actinomycetes; Mycobacteriales; OC Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex. OX NCBI_TaxID=233413; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-935 / AF2122/97; RX PubMed=12788972; DOI=10.1073/pnas.1130426100; RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M., RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B., RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J., RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.; RT "The complete genome sequence of Mycobacterium bovis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION. RC STRAIN=ATCC BAA-935 / AF2122/97; RX PubMed=28385856; DOI=10.1128/genomea.00157-17; RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R., RA Robbe-Austerman S., Gordon S.V.; RT "Updated reference genome sequence and annotation of Mycobacterium bovis RT AF2122/97."; RL Genome Announc. 5:E00157-E00157(2017). 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 to yield (R)-2,3-dihydroxy-isovalerate. CC {ECO:0000255|HAMAP-Rule:MF_00435}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (2S)-2- CC acetolactate + NADPH + H(+); Xref=Rhea:RHEA:22068, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:49072, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:58476; EC=1.1.1.86; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00435}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2- CC ethyl-2-hydroxy-3-oxobutanoate + NADPH + H(+); Xref=Rhea:RHEA:13493, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:49256, ChEBI:CHEBI:49258, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.86; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00435}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00435}; CC Note=Binds 2 magnesium ions per subunit. {ECO:0000255|HAMAP- CC Rule:MF_00435}; 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}. 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; LT708304; SIU01650.1; -; Genomic_DNA. DR RefSeq; WP_003899581.1; NC_002945.4. DR AlphaFoldDB; P65150; -. DR SMR; P65150; -. DR GeneID; 45426991; -. DR KEGG; mbo:BQ2027_MB3026C; -. DR PATRIC; fig|233413.5.peg.3326; -. DR UniPathway; UPA00047; UER00056. DR UniPathway; UPA00049; UER00060. DR Proteomes; UP000001419; Chromosome. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. 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:0009099; P:L-valine biosynthetic process; IEA:UniProtKB-UniRule. DR FunFam; 3.40.50.720:FF:000023; Ketol-acid reductoisomerase (NADP(+)); 1. DR Gene3D; 6.10.240.10; -; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. 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 NCBIfam; TIGR00465; ilvC; 1. DR NCBIfam; NF004017; PRK05479.1; 1. DR PANTHER; PTHR21371; KETOL-ACID REDUCTOISOMERASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR21371:SF1; KETOL-ACID REDUCTOISOMERASE, MITOCHONDRIAL; 1. DR Pfam; PF01450; KARI_C; 1. DR Pfam; PF07991; KARI_N; 1. DR PIRSF; PIRSF000116; IlvC_gammaproteo; 1. DR SUPFAM; SSF48179; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS51851; KARI_C; 1. DR PROSITE; PS51850; KARI_N; 1. PE 3: Inferred from homology; KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Magnesium; KW Metal-binding; NADP; Oxidoreductase; Reference proteome. FT CHAIN 1..333 FT /note="Ketol-acid reductoisomerase (NADP(+))" FT /id="PRO_0000151330" FT DOMAIN 1..179 FT /note="KARI N-terminal Rossmann" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01197" FT DOMAIN 180..325 FT /note="KARI C-terminal knotted" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01198" FT ACT_SITE 105 FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 22..25 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 45 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 48 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 50 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 80..83 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 131 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 188 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 188 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 192 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 224 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 228 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" FT BINDING 249 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435" SQ SEQUENCE 333 AA; 36090 MW; 49669E3EDACE25EC CRC64; MFYDDDADLS IIQGRKVGVI GYGSQGHAHS LSLRDSGVQV RVGLKQGSRS RPKVEEQGLD VDTPAEVAKW ADVVMVLAPD TAQAEIFAGD IEPNLKPGDA LFFGHGLNVH FGLIKPPADV AVAMVAPKGP GHLVRRQFVD GKGVPCLVAV EQDPRGDGLA LALSYAKAIG GTRAGVIKTT FKDETETDLF GEQTVLCGGT EELVKAGFEV MVEAGYPAEL AYFEVLHELK LIVDLMYEGG LARMYYSVSD TAEFGGYLSG PRVIDAGTKE RMRDILREIQ DGSFVHKLVA DVEGGNKQLE ELRRQNAEHP IEVVGKKLRD LMSWVDRPIT ETA //