ILVC_MYCTU
ID ILVC_MYCTU Reviewed; 337 AA.
AC P9WKJ7; L0TE69; O53248; P65149;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 2.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=Ketol-acid reductoisomerase (NADP(+)) {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:26876563};
DE Short=KARI {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:26876563};
DE EC=1.1.1.86 {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000269|PubMed:26876563};
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:26876563};
DE AltName: Full=Ketol-acid reductoisomerase type I {ECO:0000255|HAMAP-Rule:MF_00435, ECO:0000303|PubMed:26876563};
GN Name=ilvC {ECO:0000255|HAMAP-Rule:MF_00435}; OrderedLocusNames=Rv3001c;
GN ORFNames=MTV012.15c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP PROTEIN SEQUENCE OF 2-20, AND SEQUENCE REVISION TO N-TERMINUS.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2022).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) OF 5-337 IN COMPLEX WITH MAGNESIUM
RP IONS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP COFACTOR, ACTIVITY REGULATION, SUBSTRATE SPECIFICITY, AND SUBUNIT.
RX PubMed=26876563; DOI=10.1111/febs.13672;
RA Lv Y., Kandale A., Wun S.J., McGeary R.P., Williams S.J., Kobe B.,
RA Sieber V., Schembri M.A., Schenk G., Guddat L.W.;
RT "Crystal structure of Mycobacterium tuberculosis ketol-acid
RT reductoisomerase at 1.0 A resolution - a potential target for anti-
RT tuberculosis drug discovery.";
RL FEBS J. 283:1184-1196(2016).
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. It is also
CC able to use 3-hydroxypyruvate (HP). {ECO:0000269|PubMed:26876563}.
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:0000269|PubMed:26876563};
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:26876563};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_00435, ECO:0000269|PubMed:26876563};
CC -!- ACTIVITY REGULATION: Inhibited by N-hydroxy-N-isopropyloxamate (IpOHA).
CC {ECO:0000269|PubMed:26876563}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.1 uM for S2AL {ECO:0000269|PubMed:26876563};
CC KM=7.4 uM for NADPH (with HP as substrate)
CC {ECO:0000269|PubMed:26876563};
CC KM=7.7 uM for NADPH (with S2AL as substrate)
CC {ECO:0000269|PubMed:26876563};
CC KM=110 uM for HP {ECO:0000269|PubMed:26876563};
CC Note=kcat is 12.5 sec(-1) for reductoisomerase activity with HP as
CC substrate. kcat is 1.4 sec(-1) for reductoisomerase activity with
CC S2AL as substrate. {ECO:0000269|PubMed:26876563};
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:26876563}.
CC -!- SIMILARITY: Belongs to the ketol-acid reductoisomerase family.
CC {ECO:0000255|HAMAP-Rule:MF_00435}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP45807.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000269|PubMed:34915127};
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DR EMBL; AL123456; CCP45807.1; ALT_INIT; Genomic_DNA.
DR PIR; D70855; D70855.
DR RefSeq; NP_217517.3; NC_000962.3.
DR PDB; 4YPO; X-ray; 1.00 A; A/B=5-337.
DR PDBsum; 4YPO; -.
DR AlphaFoldDB; P9WKJ7; -.
DR SMR; P9WKJ7; -.
DR STRING; 83332.Rv3001c; -.
DR PaxDb; P9WKJ7; -.
DR DNASU; 887483; -.
DR GeneID; 887483; -.
DR KEGG; mtu:Rv3001c; -.
DR PATRIC; fig|83332.12.peg.3350; -.
DR TubercuList; Rv3001c; -.
DR eggNOG; COG0059; Bacteria.
DR BRENDA; 1.1.1.86; 3445.
DR UniPathway; UPA00047; UER00056.
DR UniPathway; UPA00049; UER00060.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004455; F:ketol-acid reductoisomerase activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0009099; P:valine biosynthetic process; IBA:GO_Central.
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; Direct protein sequencing;
KW Magnesium; Metal-binding; NADP; Oxidoreductase; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:34915127"
FT CHAIN 2..337
FT /note="Ketol-acid reductoisomerase (NADP(+))"
FT /id="PRO_0000151329"
FT DOMAIN 3..183
FT /note="KARI N-terminal Rossmann"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01197"
FT DOMAIN 184..329
FT /note="KARI C-terminal knotted"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01198"
FT ACT_SITE 109
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 26..29
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 49
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 52
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 54
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 84..87
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT BINDING 135
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 ECO:0000269|PubMed:26876563"
FT BINDING 192
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:26876563"
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 ECO:0000269|PubMed:26876563"
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 ECO:0000269|PubMed:26876563"
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 ECO:0000269|PubMed:26876563"
FT BINDING 253
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00435"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 14..17
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 28..39
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 68..74
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 124..133
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 135..143
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 162..172
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:4YPO"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 185..198
FT /evidence="ECO:0007829|PDB:4YPO"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 203..217
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 222..229
FT /evidence="ECO:0007829|PDB:4YPO"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 233..251
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 254..267
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 270..284
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 287..297
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:4YPO"
FT HELIX 314..323
FT /evidence="ECO:0007829|PDB:4YPO"
SQ SEQUENCE 337 AA; 36535 MW; 9EC8C8F83369C28B CRC64;
MALEMFYDDD ADLSIIQGRK VGVIGYGSQG HAHSLSLRDS GVQVRVGLKQ GSRSRPKVEE
QGLDVDTPAE VAKWADVVMV LAPDTAQAEI FAGDIEPNLK PGDALFFGHG LNVHFGLIKP
PADVAVAMVA PKGPGHLVRR QFVDGKGVPC LVAVEQDPRG DGLALALSYA KAIGGTRAGV
IKTTFKDETE TDLFGEQTVL CGGTEELVKA GFEVMVEAGY PAELAYFEVL HELKLIVDLM
YEGGLARMYY SVSDTAEFGG YLSGPRVIDA GTKERMRDIL REIQDGSFVH KLVADVEGGN
KQLEELRRQN AEHPIEVVGK KLRDLMSWVD RPITETA
