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   27-MAR-2024, entry version 120.
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; Actinomycetota; Actinomycetes; Mycobacteriales; 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=2-oxoglutarate + H(+) + N(6)-[(R)-lipoyl]-L-lysyl-
CC         [dihydrolipoyllysine-residue succinyltransferase] = CO2 + N(6)-[(R)-
CC         S(8)-succinyldihydrolipoyl]-L-lysyl-[dihydrolipoyllysine-residue
CC         succinyltransferase]; Xref=Rhea:RHEA:12188, Rhea:RHEA-COMP:10483,
CC         Rhea:RHEA-COMP:10484, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:16810, ChEBI:CHEBI:83099, ChEBI:CHEBI:83120; EC=1.2.4.2;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[2-oxoglutarate dehydrogenase
CC         complex component E2] + succinyl-CoA = CoA + N(6)-[(R)-S(8)-
CC         succinyldihydrolipoyl]-L-lysyl-[2-oxoglutarate dehydrogenase complex
CC         component E2]; Xref=Rhea:RHEA:15213, Rhea:RHEA-COMP:10581, Rhea:RHEA-
CC         COMP:10582, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:83100,
CC         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.gene:17574921; -.
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   OrthoDB; 9759785at2; -.
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   CDD; cd02016; TPP_E1_OGDC_like; 1.
DR   Gene3D; 3.40.50.12470; -; 1.
DR   Gene3D; 3.40.50.970; -; 1.
DR   Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR   Gene3D; 3.40.50.11610; Multifunctional 2-oxoglutarate metabolism enzyme, C-terminal domain; 1.
DR   Gene3D; 1.10.287.1150; TPP helical domain; 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   NCBIfam; TIGR00239; 2oxo_dh_E1; 1.
DR   PANTHER; PTHR23152:SF4; 2-OXOADIPATE DEHYDROGENASE COMPLEX COMPONENT E1; 1.
DR   PANTHER; PTHR23152; 2-OXOGLUTARATE DEHYDROGENASE; 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; SSF52777; CoA-dependent acyltransferases; 1.
DR   SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 2.
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   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         551
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         590
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         615
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         615
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         617
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         657
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         657
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         658
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         659
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         690
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         690
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         692
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1032
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
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         1101
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1104
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"
FT   BINDING         1161
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1162
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
//