ILVC_UNCAG
ID ILVC_UNCAG Reviewed; 332 AA.
AC Q64BR7;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Ketol-acid reductoisomerase (NAD(+)) {ECO:0000303|PubMed:25849365};
DE Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:25849365};
DE EC=1.1.1.382 {ECO:0000250|UniProtKB:K4LVZ1};
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 ORFNames=GZ26G2_30 {ECO:0000312|EMBL:AAU83160.1};
OS Uncultured archaeon GZfos26G2.
OC Archaea; environmental samples.
OX NCBI_TaxID=285389;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15353801; DOI=10.1126/science.1100025;
RA Hallam S.J., Putnam N., Preston C.M., Detter J.C., Rokhsar D.,
RA Richardson P.M., DeLong E.F.;
RT "Reverse methanogenesis: testing the hypothesis with environmental
RT genomics.";
RL Science 305:1457-1462(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) IN COMPLEX WITH NAD AND MAGNESIUM
RP IONS, FUNCTION, COFACTOR, AND SUBUNIT.
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 NADH to yield (R)-2,3-dihydroxy-isovalerate.
CC {ECO:0000269|PubMed:25849365}.
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:0000250|UniProtKB:K4LVZ1};
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};
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 -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25849365}.
CC -!- SIMILARITY: Belongs to the ketol-acid reductoisomerase family.
CC {ECO:0000255|HAMAP-Rule:MF_00435}.
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DR EMBL; AY714843; AAU83160.1; -; Genomic_DNA.
DR PDB; 4XDY; X-ray; 1.53 A; A/B=1-332.
DR PDBsum; 4XDY; -.
DR AlphaFoldDB; Q64BR7; -.
DR SMR; Q64BR7; -.
DR BRENDA; 1.1.1.382; 12627.
DR BRENDA; 1.1.1.86; 12627.
DR UniPathway; UPA00047; UER00056.
DR UniPathway; UPA00049; UER00060.
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; NAD;
KW Oxidoreductase.
FT CHAIN 1..332
FT /note="Ketol-acid reductoisomerase (NAD(+))"
FT /id="PRO_0000436836"
FT DOMAIN 1..186
FT /note="KARI N-terminal Rossmann"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01197"
FT DOMAIN 187..332
FT /note="KARI C-terminal knotted"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01198"
FT ACT_SITE 112
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 ECO:0000269|PubMed:25849365"
FT BINDING 46
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 55
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 87..90
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 138
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435,
FT ECO:0000269|PubMed:25849365"
FT BINDING 195
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 195
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 199
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 231
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 235
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 256
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT HELIX 6..8
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 12..16
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 18..22
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 26..37
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 56..63
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 71..77
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4XDY"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 90..97
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 127..136
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 138..146
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:4XDY"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 188..201
FT /evidence="ECO:0007829|PDB:4XDY"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 205..220
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 225..232
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 234..254
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 257..270
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 273..287
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 290..300
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 304..315
FT /evidence="ECO:0007829|PDB:4XDY"
FT HELIX 317..327
FT /evidence="ECO:0007829|PDB:4XDY"
SQ SEQUENCE 332 AA; 36857 MW; D5904ACF0CB78E4D CRC64;
MEILHDEDVD DSILRDKTIA VMGYGAQGDA QANCLKDSGI NVVIGETEIL GGNKNPSWEK
AKEDGFEVLP IDKAAEKGDV VHILLPDEVQ PAIYENQIKP QLKAGKALCF SHGFNICFKR
IVPPEDVDVI MVAPKAPGTE ERKAYLEGFG VPGLVAVKQN PSGEAREVAL AMTKAMHWTK
AGILECTFEQ ETYEDLFGEQ CVLCGGLVEL MRNGFEVLVE AGYPPEMAYF ECVHEMKLIV
DLVWQGGIKR MAEVISNTAE YGMWAVGHQI IGPEVKEKMK EALKRVENGE FANEWVDEYK
RGIPFLKASR EKMGEHQVET VGAEIRKLFA QK
