LEUD_METJA
ID LEUD_METJA Reviewed; 168 AA.
AC Q58673;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Isopropylmalate/citramalate isomerase small subunit;
DE EC=4.2.1.33;
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;
DE Short=IPMI;
DE AltName: Full=Maleate hydratase;
DE Short=Malease;
DE EC=4.2.1.31;
GN Name=leuD; OrderedLocusNames=MJ1277;
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, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP 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).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=22326391; DOI=10.1016/j.bbrc.2012.01.125;
RA Lee E.H., Cho Y.W., Hwang K.Y.;
RT "Crystal structure of LeuD from Methanococcus jannaschii.";
RL Biochem. Biophys. Res. Commun. 419:160-164(2012).
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: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 -!- 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.
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. The heterotetramer that
CC can be formed in vitro between HacA and LeuD is inactive.
CC {ECO:0000269|PubMed:17449626}.
CC -!- SIMILARITY: Belongs to the LeuD family. {ECO:0000305}.
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DR EMBL; L77117; AAB99283.1; -; Genomic_DNA.
DR PIR; D64459; D64459.
DR PDB; 3VBA; X-ray; 2.00 A; A/B/C/D/E/F=1-168.
DR PDBsum; 3VBA; -.
DR AlphaFoldDB; Q58673; -.
DR SMR; Q58673; -.
DR STRING; 243232.MJ_1277; -.
DR EnsemblBacteria; AAB99283; AAB99283; MJ_1277.
DR KEGG; mja:MJ_1277; -.
DR eggNOG; arCOG02230; Archaea.
DR HOGENOM; CLU_081378_1_1_2; -.
DR InParanoid; Q58673; -.
DR OMA; GLPIIEC; -.
DR PhylomeDB; Q58673; -.
DR BioCyc; MetaCyc:MON-13648; -.
DR BRENDA; 4.2.1.33; 3260.
DR SABIO-RK; Q58673; -.
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; IMP:CAFA.
DR GO; GO:0050075; F:maleate hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd01577; IPMI_Swivel; 1.
DR Gene3D; 3.20.19.10; -; 1.
DR HAMAP; MF_01032; LeuD_type2; 1.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR InterPro; IPR033940; IPMI_Swivel.
DR InterPro; IPR011827; LeuD_type2/HacB/DmdB.
DR Pfam; PF00694; Aconitase_C; 1.
DR TIGRFAMs; TIGR02087; LEUD_arch; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Isoleucine biosynthesis;
KW Leucine biosynthesis; Lyase; Reference proteome.
FT CHAIN 1..168
FT /note="Isopropylmalate/citramalate isomerase small subunit"
FT /id="PRO_0000141937"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 18..21
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:3VBA"
FT TURN 39..43
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 71..78
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 91..99
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:3VBA"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:3VBA"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:3VBA"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 145..153
FT /evidence="ECO:0007829|PDB:3VBA"
FT HELIX 156..165
FT /evidence="ECO:0007829|PDB:3VBA"
SQ SEQUENCE 168 AA; 18377 MW; A53C2CA883B6CCD7 CRC64;
MRSIIKGRVW KFGNNVDTDA ILPARYLVYT KPEELAQFVM TGADPDFPKK VKPGDIIVGG
KNFGCGSSRE HAPLGLKGAG ISCVIAESFA RIFYRNAINV GLPLIECKGI SEKVNEGDEL
EVNLETGEIK NLTTGEVLKG QKLPEFMMEI LEAGGLMPYL KKKMAESQ
