LEU3_MYCTU
ID LEU3_MYCTU Reviewed; 336 AA.
AC P9WKK9; L0TB88; P95313;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=3-isopropylmalate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01035, ECO:0000303|PubMed:9111927};
DE EC=1.1.1.85 {ECO:0000255|HAMAP-Rule:MF_01035, ECO:0000305|PubMed:9111927};
DE AltName: Full=3-IPM-DH {ECO:0000255|HAMAP-Rule:MF_01035};
DE AltName: Full=Beta-IPM dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01035};
DE Short=IMDH {ECO:0000255|HAMAP-Rule:MF_01035};
GN Name=leuB {ECO:0000303|PubMed:9111927}; OrderedLocusNames=Rv2995c;
GN ORFNames=MTV012.09;
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 [GENOMIC DNA].
RX PubMed=9111927; DOI=10.1080/15216549700201701;
RA Han M.Y., Son M.Y., Lee S.H., Kim J.K., Huh J.S., Kim J.H., Choe I.S.,
RA Chung T.W., Choe Y.K.;
RT "Molecular cloning of the leuB genes from Mycobacterium bovis BCG and
RT Mycobacterium tuberculosis.";
RL Biochem. Mol. Biol. Int. 41:657-663(1997).
RN [2]
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 [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 (1.65 ANGSTROMS) OF 2-336, AND SUBUNIT.
RX PubMed=15663922; DOI=10.1016/j.jmb.2004.11.059;
RA Singh R.K., Kefala G., Janowski R., Mueller-Dieckmann C., von Kries J.-P.,
RA Weiss M.S.;
RT "The high-resolution Structure of LeuB (Rv2995c) from Mycobacterium
RT tuberculosis.";
RL J. Mol. Biol. 346:1-11(2005).
CC -!- FUNCTION: Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-
CC methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-
CC oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate.
CC {ECO:0000255|HAMAP-Rule:MF_01035}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate
CC + CO2 + NADH; Xref=Rhea:RHEA:32271, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17865, ChEBI:CHEBI:35121, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.85; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01035, ECO:0000305|PubMed:9111927};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01035};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01035};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01035};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4. {ECO:0000255|HAMAP-
CC Rule:MF_01035}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01035,
CC ECO:0000269|PubMed:15663922}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01035}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. LeuB type 2 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_01035, ECO:0000305}.
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DR EMBL; U78887; AAC45174.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45800.1; -; Genomic_DNA.
DR PIR; F70854; F70854.
DR RefSeq; NP_217511.1; NC_000962.3.
DR RefSeq; WP_003899576.1; NZ_NVQJ01000041.1.
DR PDB; 1W0D; X-ray; 1.65 A; A/B/C/D=2-336.
DR PDB; 2G4O; X-ray; 2.00 A; A/B/C/D=2-336.
DR PDBsum; 1W0D; -.
DR PDBsum; 2G4O; -.
DR AlphaFoldDB; P9WKK9; -.
DR SMR; P9WKK9; -.
DR STRING; 83332.Rv2995c; -.
DR PaxDb; P9WKK9; -.
DR DNASU; 888182; -.
DR GeneID; 888182; -.
DR KEGG; mtu:Rv2995c; -.
DR TubercuList; Rv2995c; -.
DR eggNOG; COG0473; Bacteria.
DR OMA; EYDLGAR; -.
DR PhylomeDB; P9WKK9; -.
DR BRENDA; 1.1.1.85; 3445.
DR UniPathway; UPA00048; UER00072.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
DR HAMAP; MF_01035; LeuB_type2; 1.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR023698; LeuB_actb.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Cytoplasm; Leucine biosynthesis;
KW Magnesium; Manganese; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..336
FT /note="3-isopropylmalate dehydrogenase"
FT /id="PRO_0000083803"
FT BINDING 87
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 121
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 211
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 211
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 235
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 239
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT BINDING 271..283
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT SITE 128
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT SITE 178
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01035"
FT STRAND 2..9
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 12..26
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 39..45
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 51..57
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 60..67
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 83..89
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 116..122
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:2G4O"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 152..168
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:1W0D"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 183..197
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 203..209
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 231..244
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:1W0D"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:1W0D"
FT TURN 277..280
FT /evidence="ECO:0007829|PDB:2G4O"
FT HELIX 285..297
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 301..317
FT /evidence="ECO:0007829|PDB:1W0D"
FT HELIX 325..334
FT /evidence="ECO:0007829|PDB:1W0D"
SQ SEQUENCE 336 AA; 35306 MW; E78718100CCA5B42 CRC64;
MKLAIIAGDG IGPEVTAEAV KVLDAVVPGV QKTSYDLGAR RFHATGEVLP DSVVAELRNH
DAILLGAIGD PSVPSGVLER GLLLRLRFEL DHHINLRPAR LYPGVASPLS GNPGIDFVVV
REGTEGPYTG NGGAIRVGTP NEVATEVSVN TAFGVRRVVA DAFERARRRR KHLTLVHKTN
VLTFAGGLWL RTVDEVGECY PDVEVAYQHV DAATIHMITD PGRFDVIVTD NLFGDIITDL
AAAVCGGIGL AASGNIDATR ANPSMFEPVH GSAPDIAGQG IADPTAAIMS VALLLSHLGE
HDAAARVDRA VEAHLATRGS ERLATSDVGE RIAAAL
