LEU3_ACIFR
ID LEU3_ACIFR Reviewed; 358 AA.
AC Q56268;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=3-isopropylmalate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000303|PubMed:8282728};
DE EC=1.1.1.85 {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000269|PubMed:8282728};
DE AltName: Full=3-IPM-DH {ECO:0000255|HAMAP-Rule:MF_01033};
DE AltName: Full=Beta-IPM dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01033};
DE Short=IMDH {ECO:0000255|HAMAP-Rule:MF_01033};
GN Name=leuB {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000303|PubMed:8282728};
OS Acidithiobacillus ferrooxidans (Thiobacillus ferrooxidans).
OC Bacteria; Proteobacteria; Acidithiobacillia; Acidithiobacillales;
OC Acidithiobacillaceae; Acidithiobacillus.
OX NCBI_TaxID=920;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=AP19-3;
RX PubMed=8282728; DOI=10.1093/oxfordjournals.jbchem.a124183;
RA Kawaguchi H., Inagaki K., Kuwata Y., Tanaka H., Tano T.;
RT "3-isopropylmalate dehydrogenase from chemolithoautotroph Thiobacillus
RT ferrooxidans: DNA sequence, enzyme purification, and characterization.";
RL J. Biochem. 114:370-377(1993).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND
RP MAGNESIUM IONS, AND SUBUNIT.
RC STRAIN=AP19-3;
RX PubMed=9739088; DOI=10.1016/s0969-2126(98)00099-9;
RA Imada K., Inagaki K., Matsunami H., Kawaguchi H., Tanaka H., Tanaka N.,
RA Namba K.;
RT "Structure of 3-isopropylmalate dehydrogenase in complex with 3-
RT isopropylmalate at 2.0-A resolution: the role of Glu88 in the unique
RT substrate-recognition mechanism.";
RL Structure 6:971-982(1998).
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 Can also use D-malate and L-malate, with lower efficiency.
CC {ECO:0000269|PubMed:8282728}.
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_01033, ECO:0000269|PubMed:8282728};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01033};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01033};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01033};
CC -!- ACTIVITY REGULATION: The presence of K(+) or NH4(+) is essential for
CC activity. {ECO:0000269|PubMed:8282728}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=26 uM for 3-isopropylmalate {ECO:0000269|PubMed:8282728};
CC KM=0.8 mM for NAD {ECO:0000269|PubMed:8282728};
CC KM=4 mM for D-malate {ECO:0000269|PubMed:8282728};
CC KM=12 mM for L-malate {ECO:0000269|PubMed:8282728};
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:8282728};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius.
CC {ECO:0000269|PubMed:8282728};
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_01033}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01033,
CC ECO:0000269|PubMed:8282728, ECO:0000269|PubMed:9739088}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01033}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. LeuB type 1 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_01033, ECO:0000305}.
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; D14585; BAA03437.1; -; Genomic_DNA.
DR PIR; JX0286; JX0286.
DR PDB; 1A05; X-ray; 2.00 A; A/B=1-358.
DR PDBsum; 1A05; -.
DR AlphaFoldDB; Q56268; -.
DR SMR; Q56268; -.
DR STRING; 380394.Lferr_1732; -.
DR DrugBank; DB04279; 3-Isopropylmalic Acid.
DR BRENDA; 1.1.1.85; 91.
DR UniPathway; UPA00048; UER00072.
DR EvolutionaryTrace; Q56268; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:UniProtKB-UniRule.
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_01033; LeuB_type1; 1.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR004429; Isopropylmalate_DH.
DR PANTHER; PTHR42979; PTHR42979; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00169; leuB; 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; Metal-binding; NAD; Oxidoreductase.
FT CHAIN 1..358
FT /note="3-isopropylmalate dehydrogenase"
FT /id="PRO_0000083777"
FT BINDING 75..88
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033,
FT ECO:0000269|PubMed:9739088"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033,
FT ECO:0000269|PubMed:9739088"
FT BINDING 133
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033,
FT ECO:0000269|PubMed:9739088"
FT BINDING 222
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:9739088,
FT ECO:0007744|PDB:1A05"
FT BINDING 222
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033,
FT ECO:0000269|PubMed:9739088"
FT BINDING 246
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:9739088,
FT ECO:0007744|PDB:1A05"
FT BINDING 250
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 279..291
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT SITE 140
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033,
FT ECO:0000305|PubMed:9739088"
FT SITE 190
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033,
FT ECO:0000305|PubMed:9739088"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 13..31
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 43..50
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 56..64
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1A05"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 153..163
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 164..179
FT /evidence="ECO:0007829|PDB:1A05"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 183..189
FT /evidence="ECO:0007829|PDB:1A05"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 195..207
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 221..230
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 242..254
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:1A05"
FT STRAND 272..278
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:1A05"
FT TURN 285..288
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 293..305
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 310..325
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:1A05"
FT HELIX 343..352
FT /evidence="ECO:0007829|PDB:1A05"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:1A05"
SQ SEQUENCE 358 AA; 38462 MW; 139AFDC3E2CD2060 CRC64;
MKKIAIFAGD GIGPEIVAAA RQVLDAVDQA AHLGLRCTEG LVGGAALDAS DDPLPAASLQ
LAMAADAVIL GAVGGPRWDA YPPAKRPEQG LLRLRKGLDL YANLRPAQIF PQLLDASPLR
PELVRDVDIL VVRELTGDIY FGQPRGLEVI DGKRRGFNTM VYDEDEIRRI AHVAFRAAQG
RRKQLCSVDK ANVLETTRLW REVVTEVARD YPDVRLSHMY VDNAAMQLIR APAQFDVLLT
GNMFGDILSD EASQLTGSIG MLPSASLGEG RAMYEPIHGS APDIAGQDKA NPLATILSVA
MMLRHSLNAE PWAQRVEAAV QRVLDQGLRT ADIAAPGTPV IGTKAMGAAV VNALNLKD
