LEUC_METJA
ID LEUC_METJA Reviewed; 424 AA.
AC P81291;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Isopropylmalate/citramalate isomerase large subunit;
DE EC=4.2.1.33 {ECO:0000255|HAMAP-Rule:MF_01027};
DE EC=4.2.1.35;
DE AltName: Full=(R)-2-methylmalate dehydratase;
DE AltName: Full=(R)-citramalate dehydratase;
DE AltName: Full=3-isopropylmalate dehydratase;
DE AltName: Full=Alpha-isopropylmalate dehydratase;
DE AltName: Full=Citraconate hydratase;
DE AltName: Full=Isopropylmalate isomerase {ECO:0000255|HAMAP-Rule:MF_01027};
DE Short=IPMI {ECO:0000255|HAMAP-Rule:MF_01027};
DE AltName: Full=Maleate hydratase;
DE Short=Malease;
DE EC=4.2.1.31;
GN Name=leuC {ECO:0000255|HAMAP-Rule:MF_01027}; OrderedLocusNames=MJ0499;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=17449626; DOI=10.1128/jb.00166-07;
RA Drevland R.M., Waheed A., Graham D.E.;
RT "Enzymology and evolution of the pyruvate pathway to 2-oxobutyrate in
RT Methanocaldococcus jannaschii.";
RL J. Bacteriol. 189:4391-4400(2007).
CC -!- FUNCTION: Enzyme with broad specificity that catalyzes reversible
CC hydroxyacid isomerizations via dehydration/hydration reactions.
CC Catalyzes the isomerization between 2-isopropylmalate and 3-
CC isopropylmalate, via the formation of 2-isopropylmaleate, a step
CC involved in leucine biosynthesis. Catalyzes the isomerization between
CC 2-methylmalate and 3-methylmalate, via the formation of 2-methylmaleate
CC (citraconate), a step involved in isoleucine biosynthesis. Also
CC displays malease activity, i.e. catalyzes the hydration of maleate to
CC form (R)-malate. {ECO:0000269|PubMed:17449626}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-isopropylmalate = (2S)-2-isopropylmalate;
CC Xref=Rhea:RHEA:32287, ChEBI:CHEBI:1178, ChEBI:CHEBI:35121;
CC EC=4.2.1.33; Evidence={ECO:0000255|HAMAP-Rule:MF_01027,
CC ECO:0000269|PubMed:17449626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-citramalate = 2-methylmaleate + H2O;
CC Xref=Rhea:RHEA:22332, ChEBI:CHEBI:15377, ChEBI:CHEBI:30719,
CC ChEBI:CHEBI:30934; EC=4.2.1.35;
CC Evidence={ECO:0000269|PubMed:17449626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylmaleate + H2O = (2R,3S)-3-methylmalate;
CC Xref=Rhea:RHEA:42424, ChEBI:CHEBI:15377, ChEBI:CHEBI:30719,
CC ChEBI:CHEBI:58511; EC=4.2.1.35;
CC Evidence={ECO:0000269|PubMed:17449626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-malate = H2O + maleate; Xref=Rhea:RHEA:23692,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15588, ChEBI:CHEBI:30780; EC=4.2.1.31;
CC Evidence={ECO:0000269|PubMed:17449626};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01027,
CC ECO:0000269|PubMed:17449626};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01027, ECO:0000269|PubMed:17449626};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=80 uM for 2-methylmaleate {ECO:0000269|PubMed:17449626};
CC KM=810 uM for (R)-2-methylmalate {ECO:0000269|PubMed:17449626};
CC KM=1900 uM for racemic 2-isopropylmalate
CC {ECO:0000269|PubMed:17449626};
CC KM=39 uM for racemic 3-isopropylmalate {ECO:0000269|PubMed:17449626};
CC KM=400 uM for maleate {ECO:0000269|PubMed:17449626};
CC Vmax=15 umol/min/mg enzyme for 2-methylmaleate hydration reaction
CC {ECO:0000269|PubMed:17449626};
CC Vmax=1.5 umol/min/mg enzyme for (R)-2-methylmalate dehydration
CC reaction {ECO:0000269|PubMed:17449626};
CC Vmax=4.2 umol/min/mg enzyme for 2-isopropylmalate dehydration
CC reaction {ECO:0000269|PubMed:17449626};
CC Vmax=1.8 umol/min/mg enzyme for 3-isopropylmalate dehydration
CC reaction {ECO:0000269|PubMed:17449626};
CC Vmax=34 umol/min/mg enzyme for maleate hydration reaction
CC {ECO:0000269|PubMed:17449626};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:17449626};
CC Temperature dependence:
CC Optimum temperature is 70 degrees Celsius.
CC {ECO:0000269|PubMed:17449626};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 2/4. {ECO:0000255|HAMAP-
CC Rule:MF_01027}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; 2-
CC oxobutanoate from pyruvate: step 2/3.
CC -!- SUBUNIT: Heterotetramer of 2 LeuC and 2 LeuD. Cannot form a complex
CC with HacB. {ECO:0000269|PubMed:17449626}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family. LeuC type 2
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_01027}.
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DR EMBL; L77117; AAB98487.1; -; Genomic_DNA.
DR PIR; C64362; C64362.
DR RefSeq; WP_010870000.1; NC_000909.1.
DR PDB; 4KP1; X-ray; 1.80 A; A=1-424.
DR PDB; 4NQY; X-ray; 2.60 A; A/B=1-424.
DR PDBsum; 4KP1; -.
DR PDBsum; 4NQY; -.
DR AlphaFoldDB; P81291; -.
DR SMR; P81291; -.
DR STRING; 243232.MJ_0499; -.
DR DNASU; 1451361; -.
DR EnsemblBacteria; AAB98487; AAB98487; MJ_0499.
DR GeneID; 1451361; -.
DR KEGG; mja:MJ_0499; -.
DR eggNOG; arCOG01698; Archaea.
DR HOGENOM; CLU_006714_3_4_2; -.
DR InParanoid; P81291; -.
DR OMA; CNMSIEM; -.
DR OrthoDB; 15714at2157; -.
DR PhylomeDB; P81291; -.
DR BioCyc; MetaCyc:MON-13647; -.
DR BRENDA; 4.2.1.33; 3260.
DR BRENDA; 4.2.1.36; 3260.
DR SABIO-RK; P81291; -.
DR UniPathway; UPA00047; UER00067.
DR UniPathway; UPA00048; UER00071.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0047508; F:(R)-2-methylmalate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0003861; F:3-isopropylmalate dehydratase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0050075; F:maleate hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd01583; IPMI; 1.
DR Gene3D; 3.30.499.10; -; 2.
DR HAMAP; MF_01027; LeuC_type2; 1.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR011826; HAcnase/IPMdehydase_lsu_prok.
DR InterPro; IPR006251; Homoacnase/IPMdehydase_lsu.
DR InterPro; IPR033941; IPMI_cat.
DR Pfam; PF00330; Aconitase; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01343; hacA_fam; 1.
DR TIGRFAMs; TIGR02086; IPMI_arch; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Iron; Iron-sulfur;
KW Isoleucine biosynthesis; Leucine biosynthesis; Lyase; Metal-binding;
KW Reference proteome.
FT CHAIN 1..424
FT /note="Isopropylmalate/citramalate isomerase large subunit"
FT /id="PRO_0000076869"
FT BINDING 304
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01027"
FT BINDING 365
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01027"
FT BINDING 368
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01027"
FT HELIX 5..14
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 38..48
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 73..89
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:4NQY"
FT HELIX 102..108
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 125..131
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 140..149
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 174..185
FT /evidence="ECO:0007829|PDB:4KP1"
FT TURN 187..190
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 207..215
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 222..226
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 231..244
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 262..268
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:4NQY"
FT HELIX 309..321
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 330..333
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 338..346
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 349..355
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 365..369
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:4NQY"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:4KP1"
FT STRAND 400..403
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 406..415
FT /evidence="ECO:0007829|PDB:4KP1"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:4KP1"
SQ SEQUENCE 424 AA; 46107 MW; B4D106AE165C524C CRC64;
MGMTIVEKIL AKASGKKEVS PGDIVMANID VAMVHDITGP LTVNTLKEYG IEKVWNPEKI
VILFDHQVPA DSIKAAENHI LMRKFVKEQG IKYFYDIREG VCHQVLPEKG HVAPGEVVVG
ADSHTCTHGA FGAFATGIGS TDMAHVFATG KLWFKVPETI YFNITGDLQP YVTSKDVILS
IIGEVGVDGA TYKACQFGGE TVKKMSIASR MTMTNMAIEM GGKTGIIEPD EKTIQYVKEA
MKKHGTERPF EVIKGDEDAE FAEVYEIEAD KIEPVFACPH NVDNVKQARE VAGKPIDQVF
IGSCTNGRLE DLRMAIKIIE KHGGIADDVR VVVTPASREE YLKALKEGII EKFLKYGCVV
TNPSCSACMG SLYGVLGPGE VCVSTSNRNF RGRQGSLEAE IYLASPITAA ACAVKGELVD
PRDL
