KGD_MYCLE
ID KGD_MYCLE Reviewed; 1238 AA.
AC Q9CC97;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Multifunctional 2-oxoglutarate metabolism enzyme;
DE AltName: Full=2-hydroxy-3-oxoadipate synthase;
DE Short=HOA synthase;
DE Short=HOAS;
DE EC=2.2.1.5;
DE AltName: Full=2-oxoglutarate carboxy-lyase;
DE AltName: Full=2-oxoglutarate decarboxylase;
DE AltName: Full=Alpha-ketoglutarate decarboxylase;
DE Short=KG decarboxylase;
DE Short=KGD;
DE EC=4.1.1.71;
DE AltName: Full=Alpha-ketoglutarate-glyoxylate carboligase;
DE Includes:
DE RecName: Full=2-oxoglutarate dehydrogenase E1 component;
DE Short=ODH E1 component;
DE EC=1.2.4.2;
DE AltName: Full=Alpha-ketoglutarate dehydrogenase E1 component;
DE Short=KDH E1 component;
DE Includes:
DE RecName: Full=Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex;
DE EC=2.3.1.61;
DE AltName: Full=2-oxoglutarate dehydrogenase complex E2 component;
DE Short=ODH E2 component;
DE Short=OGDC-E2;
DE AltName: Full=Dihydrolipoamide succinyltransferase;
GN Name=kgd; OrderedLocusNames=ML1095;
OS Mycobacterium leprae (strain TN).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=272631;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=TN;
RX PubMed=11234002; DOI=10.1038/35059006;
RA Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,
RA Wheeler P.R., Honore N., Garnier T., Churcher C.M., Harris D.E.,
RA Mungall K.L., Basham D., Brown D., Chillingworth T., Connor R.,
RA Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A., Hamlin N.,
RA Holroyd S., Hornsby T., Jagels K., Lacroix C., Maclean J., Moule S.,
RA Murphy L.D., Oliver K., Quail M.A., Rajandream M.A., Rutherford K.M.,
RA Rutter S., Seeger K., Simon S., Simmonds M., Skelton J., Squares R.,
RA Squares S., Stevens K., Taylor K., Whitehead S., Woodward J.R.,
RA Barrell B.G.;
RT "Massive gene decay in the leprosy bacillus.";
RL Nature 409:1007-1011(2001).
CC -!- FUNCTION: Shows three enzymatic activities that share a first common
CC step, the attack of thiamine-PP on 2-oxoglutarate (alpha-ketoglutarate,
CC KG), leading to the formation of an enamine-thiamine-PP intermediate
CC upon decarboxylation. Thus, displays KGD activity, catalyzing the
CC decarboxylation from five-carbon 2-oxoglutarate to four-carbon
CC succinate semialdehyde (SSA). Also catalyzes C-C bond formation between
CC the activated aldehyde formed after decarboxylation of alpha-
CC ketoglutarate and the carbonyl of glyoxylate (GLX), to yield 2-hydroxy-
CC 3-oxoadipate (HOA), which spontaneously decarboxylates to form 5-
CC hydroxylevulinate (HLA). And is also a component of the 2-oxoglutarate
CC dehydrogenase (ODH) complex, that catalyzes the overall conversion of
CC 2-oxoglutarate to succinyl-CoA and CO(2). The KG decarboxylase and KG
CC dehydrogenase reactions provide two alternative, tightly regulated,
CC pathways connecting the oxidative and reductive branches of the TCA
CC cycle (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + glyoxylate + H(+) = 2-hydroxy-3-oxoadipate +
CC CO2; Xref=Rhea:RHEA:14341, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:36655, ChEBI:CHEBI:57712; EC=2.2.1.5;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + H(+) = CO2 + succinate semialdehyde;
CC Xref=Rhea:RHEA:10524, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57706; EC=4.1.1.71;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-lipoyl-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + 2-oxoglutarate + H(+) = (R)-N(6)-(S(8)-
CC succinyldihydrolipoyl)-L-lysyl-[dihydrolipoyllysine-residue
CC succinyltransferase] + CO2; Xref=Rhea:RHEA:12188, Rhea:RHEA-
CC COMP:10483, Rhea:RHEA-COMP:10484, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:83099,
CC ChEBI:CHEBI:83120; EC=1.2.4.2;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[2-oxoglutarate dehydrogenase
CC complex component E2] + succinyl-CoA = (R)-N(6)-(S(8)-
CC succinyldihydrolipoyl)-L-lysyl-[2-oxoglutarate dehydrogenase complex
CC component E2] + CoA; Xref=Rhea:RHEA:15213, Rhea:RHEA-COMP:10581,
CC Rhea:RHEA-COMP:10582, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292,
CC ChEBI:CHEBI:83100, ChEBI:CHEBI:83120; EC=2.3.1.61;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Alpha-ketoglutarate dehydrogenase and
CC decarboxylase activities are inhibited by unphosphorylated GarA, and
CC allosterically activated by acetyl-CoA, the main substrate of the TCA
CC cycle. {ECO:0000250}.
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; succinate
CC from 2-oxoglutarate (transferase route): step 1/2.
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; succinyl-
CC CoA from 2-oxoglutarate (dehydrogenase route): step 1/1.
CC -!- SUBUNIT: Homodimer. The 2-oxoglutarate dehydrogenase (ODH) complex
CC contains multiple copies of three enzymatic components: 2-oxoglutarate
CC dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and
CC lipoamide dehydrogenase (E3) (By similarity). {ECO:0000250}.
CC -!- DOMAIN: Is a fusion protein with two major domains exhibiting
CC structural features of an E1 and E2 protein, and a short sequence
CC stretch of E1 localized at the N-terminus, which is connected by a
CC linker region to the rest of the protein. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family. Kgd
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAC31476.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL583920; CAC31476.1; ALT_INIT; Genomic_DNA.
DR PIR; A87046; A87046.
DR RefSeq; NP_301802.2; NC_002677.1.
DR RefSeq; WP_010908126.1; NC_002677.1.
DR AlphaFoldDB; Q9CC97; -.
DR SMR; Q9CC97; -.
DR STRING; 272631.ML1095; -.
DR EnsemblBacteria; CAC31476; CAC31476; CAC31476.
DR KEGG; mle:ML1095; -.
DR PATRIC; fig|272631.5.peg.1959; -.
DR Leproma; ML1095; -.
DR eggNOG; COG0508; Bacteria.
DR eggNOG; COG0567; Bacteria.
DR HOGENOM; CLU_004709_1_0_11; -.
DR UniPathway; UPA00223; UER00997.
DR UniPathway; UPA00223; UER01001.
DR Proteomes; UP000000806; Chromosome.
DR GO; GO:0050439; F:2-hydroxy-3-oxoadipate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008683; F:2-oxoglutarate decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0004149; F:dihydrolipoyllysine-residue succinyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProt.
DR GO; GO:0004591; F:oxoglutarate dehydrogenase (succinyl-transferring) activity; IEA:UniProtKB-EC.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:InterPro.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.50.11610; -; 1.
DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
DR InterPro; IPR032106; 2-oxogl_dehyd_N.
DR InterPro; IPR011603; 2oxoglutarate_DH_E1.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001017; DH_E1.
DR InterPro; IPR031717; KGD_C.
DR InterPro; IPR042179; KGD_C_sf.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR005475; Transketolase-like_Pyr-bd.
DR PANTHER; PTHR23152; PTHR23152; 1.
DR Pfam; PF00198; 2-oxoacid_dh; 1.
DR Pfam; PF16078; 2-oxogl_dehyd_N; 1.
DR Pfam; PF00676; E1_dh; 1.
DR Pfam; PF16870; OxoGdeHyase_C; 1.
DR Pfam; PF02779; Transket_pyr; 1.
DR PIRSF; PIRSF000157; Oxoglu_dh_E1; 1.
DR SMART; SM00861; Transket_pyr; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
DR TIGRFAMs; TIGR00239; 2oxo_dh_E1; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Allosteric enzyme; Coiled coil; Decarboxylase; Lyase;
KW Magnesium; Metal-binding; Multifunctional enzyme; Oxidoreductase;
KW Reference proteome; Thiamine pyrophosphate; Transferase;
KW Tricarboxylic acid cycle.
FT CHAIN 1..1238
FT /note="Multifunctional 2-oxoglutarate metabolism enzyme"
FT /id="PRO_0000310716"
FT REGION 1..41
FT /note="2-oxoglutarate dehydrogenase E1, N-terminal part"
FT REGION 42..97
FT /note="Linker"
FT REGION 44..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 98..346
FT /note="Succinyltransferase E2"
FT REGION 347..1238
FT /note="2-oxoglutarate dehydrogenase E1, C-terminal part"
FT REGION 1101..1104
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT REGION 1161..1162
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT COILED 795..825
FT /evidence="ECO:0000255"
FT COMPBIAS 47..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 325
FT /note="Proton acceptor; for succinyltransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 550..551
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 590
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 615..617
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 615
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 657..659
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 657
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 690
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 692
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 964
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 1032
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 1050
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT BINDING 1066
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT BINDING 1154
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
SQ SEQUENCE 1238 AA; 137020 MW; 62B154E8A1D9A0E8 CRC64;
MANISSPFGQ NEWLVEEMYR KFRDDPSSVD PSWHEFLVDY NPESTAEPVL TDPTSTDKQP
SATPQAKPAA AADPVASRAK PATTPTVANG TAAGSAAAPA KTTTTPPIEG DELQVLRGAA
AVVVKNMSAS LDVPTATSVR AVPAKLMIDN RTVINNQLKR NRGGKISFTH LLGYALVQAV
KKFPNINRHY AEIDGKPIAV TPAHTNLGLA IDLQGKDGKR SLVVAGIKRC EELRFAQFVT
AYEDIVRRAR DGKLTAEDFA GVTISLTNPG TIGTVHSVPR LMTGQGAIIG VGAMEYPAEF
QGASAERIAE LGIGKLITLT STYDHRIIQG AESGDFLRTI HEMVLSDSFW DEIFRELSIP
YLPVRWRTDN PDSIVDKNAR VMELIAAYRN RGHLMADIDP LRLDNTRFRS HPDLDLLTHG
LTLWDLDRVF KVNGFGGWKY KKLRDVLGLL RDAYCRHIGV EYTHILDPEQ QEWLQQRVET
KNVKPTVAEQ KYILSKLNAA EAFETFLHTK YVGQKRFSLE GAESVIPMMD AAIDQCAKHG
LDEVVIGMPH RGRLNVLANI VGKPYSQIFT EFEGNLNPTL AHSSGDVKYH LGATGLYLQM
FGDNDIQVSL TANPSHLEAV DPVLEGLVRA KQDLLNKDTN GNQDEAFSVV PMMLHGDAAF
AGQGVVAETL NLANLPGYRV GGTIHIIVNN QIGFTTAPEY SRSSEYCTDV AKMIGAPIFH
VNGDDPEACV WVAKLAVDFR QRFKKDVVID MLCYRRRGHN EGDDPSMTNP YMYDVVDTKR
GARKSYTEAL IGRGDISLKE AEDALRDYQG QLERVFNEVR DLEKHGVQPS ESVESDQMIP
AGLSTAVDKA LLARIGDAFL AVPEGFTVHP RVQPVLEKRR EMAYEGKIDW AFAELLALGS
LVAEGKLVRL SGQDTKRGTF SQRHSVIIDR HTGEEFTPLQ LLANNPDGSP TGGKFLVYNS
PLSEYAAVGF EYGYTVGNPD AVVLWEAQFG DFVNGAQSII DEFINSGEAK WGQLSTVVLL
LPHGHEGQGP DHTSGRIERF LQLWAEGSMT FAVPSTPSNY FHLLRRHALD GIKRPLIVFT
PKSMLRNKAA VSDIKDFTEI KFRSVLEEPT YEDSIDDRSK VTRVLLTCGK LYYELAARKI
KDNRDDVAIV RIEQLAPLPR RRLGETLDRY ENAKEFFWVQ EEPANQGAWP RFGLELPELL
PRLTGIKRIS RRAMSAPSSG SSKVHAVEQQ EILDTAFG
