ILVC_ALIAD
ID ILVC_ALIAD Reviewed; 344 AA.
AC C8WR67;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Ketol-acid reductoisomerase (NADP(+)) {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25849365};
DE Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25849365};
DE EC=1.1.1.86 {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000305|PubMed:25849365};
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:25849365};
DE AltName: Full=Ketol-acid reductoisomerase type I {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25849365};
GN Name=ilvC {ECO:0000255|HAMAP-Rule:MF_00435};
GN OrderedLocusNames=Aaci_2227 {ECO:0000312|EMBL:ACV59236.1};
OS Alicyclobacillus acidocaldarius subsp. acidocaldarius (strain ATCC 27009 /
OS DSM 446 / BCRC 14685 / JCM 5260 / KCTC 1825 / NBRC 15652 / NCIMB 11725 /
OS NRRL B-14509 / 104-IA) (Bacillus acidocaldarius).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Alicyclobacillaceae;
OC Alicyclobacillus.
OX NCBI_TaxID=521098;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27009 / DSM 446 / BCRC 14685 / JCM 5260 / KCTC 1825 / NBRC
RC 15652 / NCIMB 11725 / NRRL B-14509 / 104-IA;
RG US DOE Joint Genome Institute (JGI-PGF);
RA Lucas S., Copeland A., Lapidus A., Glavina del Rio T., Dalin E., Tice H.,
RA Bruce D., Goodwin L., Pitluck S., Kyrpides N., Mavromatis K., Ivanova N.,
RA Ovchinnikova G., Chertkov O., Sims D., Brettin T., Detter J.C., Han C.,
RA Larimer F., Land M., Hauser L., Markowitz V., Cheng J.-F., Hugenholtz P.,
RA Woyke T., Wu D., Pukall R., Klenk H.-P., Eisen J.A.;
RT "The complete chromosome of Alicyclobacillus acidocaldarius subsp.
RT acidocaldarius DSM 446.";
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS AND
RP NADP ANALOG, FUNCTION, MUTAGENESIS OF ARG-48 AND SER-52, AND COFACTOR.
RX PubMed=25849365; DOI=10.1042/bj20150183;
RA Cahn J.K., Brinkmann-Chen S., Spatzal T., Wiig J.A., Buller A.R.,
RA Einsle O., Hu Y., Ribbe M.W., Arnold F.H.;
RT "Cofactor specificity motifs and the induced fit mechanism in class I
RT ketol-acid reductoisomerases.";
RL Biochem. J. 468:475-484(2015).
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, ECO:0000269|PubMed:25849365}.
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=1.1.1.86; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00435, ECO:0000305|PubMed:25849365};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-
CC ethyl-2-hydroxy-3-oxobutanoate + H(+) + NADPH; 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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00435,
CC ECO:0000269|PubMed:25849365};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_00435, ECO:0000269|PubMed:25849365};
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; CP001727; ACV59236.1; -; Genomic_DNA.
DR RefSeq; WP_012811489.1; NC_013205.1.
DR PDB; 4TSK; X-ray; 2.50 A; A=1-344.
DR PDBsum; 4TSK; -.
DR AlphaFoldDB; C8WR67; -.
DR SMR; C8WR67; -.
DR STRING; 521098.Aaci_2227; -.
DR EnsemblBacteria; ACV59236; ACV59236; Aaci_2227.
DR KEGG; aac:Aaci_2227; -.
DR eggNOG; COG0059; Bacteria.
DR HOGENOM; CLU_033821_0_1_9; -.
DR OMA; RAMFSWL; -.
DR OrthoDB; 188901at2; -.
DR BRENDA; 1.1.1.382; 14587.
DR BRENDA; 1.1.1.86; 14587.
DR UniPathway; UPA00047; UER00056.
DR UniPathway; UPA00049; UER00060.
DR Proteomes; UP000001917; 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 3D-structure; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Magnesium; Metal-binding; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..344
FT /note="Ketol-acid reductoisomerase (NADP(+))"
FT /id="PRO_0000436831"
FT DOMAIN 2..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 25..28
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 48
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 52
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 82..85
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 133
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
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 ECO:0000269|PubMed:25849365"
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 ECO:0000269|PubMed:25849365"
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 ECO:0000269|PubMed:25849365"
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"
FT MUTAGEN 48
FT /note="R->P: Inversion of the cofactor specificity from
FT NADPH to NADH."
FT /evidence="ECO:0000269|PubMed:25849365"
FT MUTAGEN 52
FT /note="S->D: Inversion of the cofactor specificity from
FT NADPH to NADH."
FT /evidence="ECO:0000269|PubMed:25849365"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 13..16
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 19..23
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 27..38
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 51..58
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 66..72
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 85..92
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 133..141
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:4TSK"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 183..196
FT /evidence="ECO:0007829|PDB:4TSK"
FT TURN 197..199
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 200..215
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 220..227
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 229..249
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 252..265
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 268..282
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 285..295
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:4TSK"
FT HELIX 312..322
FT /evidence="ECO:0007829|PDB:4TSK"
SQ SEQUENCE 344 AA; 37909 MW; 0A510D8EB2DBABC3 CRC64;
MEKIYYDADI SIQPLADKRI AVIGYGSQGH AHAQNLRDSG FDVVIGLRPG SSWAKAEADG
FRVMAVGEAV EESDVIMILL PDERQPAVYE REIRPYLTAG KALAFAHGFN IHFSQIQPPK
DVDVFMVAPK GPGHLVRRVY EAGGGVPALI AVHQDASGQA KDLALAYARG IGAGRAGILT
TTFREETETD LFGEQAVLCG GLSALIKAGF ETLVEAGYQP EIAYFECLHE MKLIVDLIYE
GGLEYMRYSI SDTAQWGDFT SGPRIINEET KKEMRRILAD IQSGAFAKSW ILENQANRPM
FNAINRRELE HPIEVVGRKL RSMMPFIKAK RPGDDRVPAT ADRA
