LEU3_SALTY
ID LEU3_SALTY Reviewed; 363 AA.
AC P37412;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=3-isopropylmalate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000303|PubMed:7590327};
DE EC=1.1.1.85 {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000269|PubMed:14087358, ECO:0000269|PubMed:4889950};
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:1730062};
GN OrderedLocusNames=STM0112;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LT2;
RX PubMed=1730062; DOI=10.1016/0167-4781(92)90493-j;
RA Andreadis A., Rosenthal E.R.;
RT "The nucleotide sequence of leuB from Salmonella typhimurium.";
RL Biochim. Biophys. Acta 1129:228-230(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION.
RC STRAIN=LT2;
RX PubMed=7590327; DOI=10.1016/0378-1119(95)00494-q;
RA Kryger G., Wallon G., Lovett S.T., Ringe D., Petsko G.A.;
RT "Revision of the amino-acid sequence of 3-isopropylmalate dehydrogenase
RT from Salmonella typhimurium by means of X-ray crystallography.";
RL Gene 164:85-87(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=LT2;
RX PubMed=14087358; DOI=10.1021/bi00905a024;
RA Burns R.O., Umbarger H.E., Gross S.R.;
RT "The biosynthesis of leucine. III. The conversion of alpha-hydroxy-beta-
RT carboxyisocaproate to alpha-ketoisocaproate.";
RL Biochemistry 2:1053-1058(1963).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=4889950; DOI=10.1016/s0021-9258(18)91884-3;
RA Parsons S.J., Burns R.O.;
RT "Purification and properties of beta-isopropylmalate dehydrogenase.";
RL J. Biol. Chem. 244:996-1003(1969).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS, AND
RP SUBUNIT.
RX PubMed=9086278; DOI=10.1006/jmbi.1996.0797;
RA Wallon G., Kryger G., Lovett S.T., Oshima T., Ringe D., Petsko G.A.;
RT "Crystal structures of Escherichia coli and Salmonella typhimurium 3-
RT isopropylmalate dehydrogenase and comparison with their thermophilic
RT counterpart from Thermus thermophilus.";
RL J. Mol. Biol. 266:1016-1031(1997).
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_01033, ECO:0000269|PubMed:14087358,
CC ECO:0000269|PubMed:4889950}.
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:14087358,
CC ECO:0000269|PubMed:4889950};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01033,
CC ECO:0000269|PubMed:14087358};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01033,
CC ECO:0000269|PubMed:14087358, ECO:0000269|PubMed:9086278};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01033};
CC -!- ACTIVITY REGULATION: Inhibited by p-hydroxymercuribenzoate and N-
CC ethylmaleimide, but not by iodoacetate or iodoacetamide.
CC {ECO:0000269|PubMed:4889950}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=19 uM for beta-isopropylmalate {ECO:0000269|PubMed:4889950};
CC KM=0.1 mM for NAD {ECO:0000269|PubMed:4889950};
CC pH dependence:
CC Optimum pH is 9.0 (PubMed:4889950). Optimum pH is 9.5
CC (PubMed:14087358). {ECO:0000269|PubMed:14087358,
CC ECO:0000269|PubMed:4889950};
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:4889950, ECO:0000269|PubMed:9086278}.
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}.
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DR EMBL; X53376; CAA37456.1; -; Genomic_DNA.
DR EMBL; U20795; AAB60185.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL19076.1; -; Genomic_DNA.
DR PIR; S20606; S20606.
DR RefSeq; NP_459117.1; NC_003197.2.
DR RefSeq; WP_000042325.1; NC_003197.2.
DR PDB; 1CNZ; X-ray; 1.76 A; A/B=1-363.
DR PDBsum; 1CNZ; -.
DR AlphaFoldDB; P37412; -.
DR SMR; P37412; -.
DR STRING; 99287.STM0112; -.
DR PaxDb; P37412; -.
DR PRIDE; P37412; -.
DR EnsemblBacteria; AAL19076; AAL19076; STM0112.
DR GeneID; 1251630; -.
DR KEGG; stm:STM0112; -.
DR PATRIC; fig|99287.12.peg.118; -.
DR HOGENOM; CLU_031953_0_3_6; -.
DR OMA; EYDLGAR; -.
DR PhylomeDB; P37412; -.
DR BioCyc; SENT99287:STM0112-MON; -.
DR BRENDA; 1.1.1.85; 5542.
DR UniPathway; UPA00048; UER00072.
DR EvolutionaryTrace; P37412; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IBA:GO_Central.
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; IBA:GO_Central.
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; Manganese; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..363
FT /note="3-isopropylmalate dehydrogenase"
FT /id="PRO_0000083743"
FT BINDING 78..91
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 138
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 227
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:9086278,
FT ECO:0007744|PDB:1CNZ"
FT BINDING 227
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 251
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 251
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:9086278,
FT ECO:0007744|PDB:1CNZ"
FT BINDING 255
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 255
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:9086278,
FT ECO:0007744|PDB:1CNZ"
FT BINDING 285..297
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT SITE 145
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT SITE 195
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT CONFLICT 32..40
FT /note="SRFDMRITT -> VLICVYH (in Ref. 1; CAA37456)"
FT /evidence="ECO:0000305"
FT CONFLICT 52..55
FT /note="NHGH -> SSGI (in Ref. 1; CAA37456)"
FT /evidence="ECO:0000305"
FT CONFLICT 81..94
FT /note="WENLPPESQPERGA -> MGKFAPGKPAGARR (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="R -> C (in Ref. 1; CAA37456)"
FT /evidence="ECO:0000305"
FT CONFLICT 311..313
FT /note="YSL -> TA (in Ref. 1; CAA37456)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="Missing (in Ref. 1; CAA37456)"
FT /evidence="ECO:0000305"
FT STRAND 5..13
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 16..34
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 47..53
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 92..102
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 125..130
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 160..168
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 169..184
FT /evidence="ECO:0007829|PDB:1CNZ"
FT TURN 185..187
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:1CNZ"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 200..213
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 247..261
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:1CNZ"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:1CNZ"
FT TURN 291..294
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 299..312
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 316..331
FT /evidence="ECO:0007829|PDB:1CNZ"
FT TURN 337..344
FT /evidence="ECO:0007829|PDB:1CNZ"
FT HELIX 348..360
FT /evidence="ECO:0007829|PDB:1CNZ"
SQ SEQUENCE 363 AA; 39513 MW; 3AEEED0A4BAB7FB4 CRC64;
MSKNYHIAVL PGDGIGPEVM AQALKVMDAV RSRFDMRITT SHYDVGGIAI DNHGHPLPKA
TVEGCEQADA ILFGSVGGPK WENLPPESQP ERGALLPLRK HFKLFSNLRP AKLYQGLEAF
CPLRADIAAN GFDILCVREL TGGIYFGQPK GREGSGQYEK AFDTEVYHRF EIERIARIAF
ESARKRRRKV TSIDKANVLQ SSILWREIVN DVAKTYPDVE LAHMYIDNAT MQLIKDPSQF
DVLLCSNLFG DILSDECAMI TGSMGMLPSA SLNEQGFGLY EPAGGSAPDI AGKNIANPIA
QILSLALLLR YSLDANDAAT AIEQAINRAL EEGVRTGDLA RGAAAVSTDE MGDIIARYVA
EGV
