ID   KGD_MYCBP               Reviewed;        1231 AA.
AC   A1KI36;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 2.
DT   27-MAR-2024, entry version 89.
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=BCG_1308c;
OS   Mycobacterium bovis (strain BCG / Pasteur 1173P2).
OC   Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=410289;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=BCG / Pasteur 1173P2;
RX   PubMed=17372194; DOI=10.1073/pnas.0700869104;
RA   Brosch R., Gordon S.V., Garnier T., Eiglmeier K., Frigui W., Valenti P.,
RA   Dos Santos S., Duthoy S., Lacroix C., Garcia-Pelayo C., Inwald J.K.,
RA   Golby P., Garcia J.N., Hewinson R.G., Behr M.A., Quail M.A., Churcher C.,
RA   Barrell B.G., Parkhill J., Cole S.T.;
RT   "Genome plasticity of BCG and impact on vaccine efficacy.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:5596-5601(2007).
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=CAL71295.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AM408590; CAL71295.1; ALT_INIT; Genomic_DNA.
DR   RefSeq; WP_010950509.1; NC_008769.1.
DR   AlphaFoldDB; A1KI36; -.
DR   SMR; A1KI36; -.
DR   KEGG; mbb:BCG_1308c; -.
DR   HOGENOM; CLU_004709_1_0_11; -.
DR   UniPathway; UPA00223; UER00997.
DR   UniPathway; UPA00223; UER01001.
DR   Proteomes; UP000001472; 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   Thiamine pyrophosphate; Transferase; Tricarboxylic acid cycle.
FT   CHAIN           1..1231
FT                   /note="Multifunctional 2-oxoglutarate metabolism enzyme"
FT                   /id="PRO_0000310715"
FT   REGION          1..41
FT                   /note="2-oxoglutarate dehydrogenase E1, N-terminal part"
FT   REGION          24..56
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          42..88
FT                   /note="Linker"
FT   REGION          89..337
FT                   /note="Succinyltransferase E2"
FT   REGION          338..1231
FT                   /note="2-oxoglutarate dehydrogenase E1, C-terminal part"
FT   COILED          787..817
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        316
FT                   /note="Proton acceptor; for succinyltransferase activity"
FT                   /evidence="ECO:0000250"
FT   BINDING         542
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         581
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         606
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         606
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         608
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         649
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         649
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         650
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         651
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         682
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         682
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         684
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1024
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1042
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1058
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1093
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1096
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1146
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1153
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   1231 AA;  135876 MW;  02D4FD5F9718C330 CRC64;
     MANISSPFGQ NEWLVEAMYR KFRDDPSSVD PSWHEFLVDY SPEPTSQPAA EPTRVTSPLV
     AERAAAAAPQ APPKPADTAA AGNGVVAALA AKTAVPPPAE GDEVAVLRGA AAAVVKNMSA
     SLEVPTATSV RAVPAKLLID NRIVINNQLK RTRGGKISFT HLLGYALVQA VKKFPNMNRH
     YTEVDGKPTA VTPAHTNLGL AIDLQGKDGK RSLVVAGIKR CETMRFAQFV TAYEDIVRRA
     RDGKLTTEDF AGVTISLTNP GTIGTVHSVP RLMPGQGAII GVGAMEYPAE FQGASEERIA
     ELGIGKLITL TSTYDHRIIQ GAESGDFLRT IHELLLSDGF WDEVFRELSI PYLPVRWSTD
     NPDSIVDKNA RVMNLIAAYR NRGHLMADTD PLRLDKARFR SHPDLEVLTH GLTLWDLDRV
     FKVDGFAGAQ YKKLRDVLGL LRDAYCRHIG VEYAHILDPE QKEWLEQRVE TKHVKPTVAQ
     QKYILSKLNA AEAFETFLQT KYVGQKRFSL EGAESVIPMM DAAIDQCAEH GLDEVVIGMP
     HRGRLNVLAN IVGKPYSQIF TEFEGNLNPS QAHGSGDVKY HLGATGLYLQ MFGDNDIQVS
     LTANPSHLEA VDPVLEGLVR AKQDLLDHGS IDSDGQRAFS VVPLMLHGDA AFAGQGVVAE
     TLNLANLPGY RVGGTIHIIV NNQIGFTTAP EYSRSSEYCT DVAKMIGAPI FHVNGDDPEA
     CVWVARLAVD FRQRFKKDVV IDMLCYRRRG HNEGDDPSMT NPYMYDVVDT KRGARKSYTE
     ALIGRGDISM KEAEDALRDY QGQLERVFNE VRELEKHGVQ PSESVESDQM IPAGLATAVD
     KSLLARIGDA FLALPNGFTA HPRVQPVLEK RREMAYEGKI DWAFGELLAL GSLVAEGKLV
     RLSGQDSRRG TFSQRHSVLI DRHTGEEFTP LQLLATNSDG SPTGGKFLVY DSPLSEYAAV
     GFEYGYTVGN PDAVVLWEAQ FGDFVNGAQS IIDEFISSGE AKWGQLSNVV LLLPHGHEGQ
     GPDHTSARIE RFLQLWAEGS MTIAMPSTPS NYFHLLRRHA LDGIQRPLIV FTPKSMLRHK
     AAVSEIKDFT EIKFRSVLEE PTYEDGIGDR NKVSRILLTS GKLYYELAAR KAKDNRNDLA
     IVRLEQLAPL PRRRLRETLD RYENVKEFFW VQEEPANQGA WPRFGLELPE LLPDKLAGIK
     RISRRAMSAP SSGSSKVHAV EQQEILDEAF G
//