ID   KGD_MYCSK               Reviewed;        1269 AA.
AC   A1UK81;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   06-FEB-2007, sequence version 1.
DT   27-MAR-2024, entry version 101.
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=Mkms_4047;
OS   Mycobacterium sp. (strain KMS).
OC   Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC   Mycobacterium.
OX   NCBI_TaxID=189918;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=KMS;
RG   US DOE Joint Genome Institute;
RA   Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA   Glavina del Rio T., Hammon N., Israni S., Dalin E., Tice H., Pitluck S.,
RA   Kiss H., Brettin T., Bruce D., Han C., Tapia R., Gilna P., Schmutz J.,
RA   Larimer F., Land M., Hauser L., Kyrpides N., Mikhailova N., Miller C.D.,
RA   Richardson P.;
RT   "Complete sequence of chromosome of Mycobacterium sp. KMS.";
RL   Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
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}.
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DR   EMBL; CP000518; ABL93239.1; -; Genomic_DNA.
DR   AlphaFoldDB; A1UK81; -.
DR   SMR; A1UK81; -.
DR   STRING; 189918.Mkms_4047; -.
DR   KEGG; mkm:Mkms_4047; -.
DR   HOGENOM; CLU_004709_1_0_11; -.
DR   OrthoDB; 9759785at2; -.
DR   UniPathway; UPA00223; UER00997.
DR   UniPathway; UPA00223; UER01001.
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..1269
FT                   /note="Multifunctional 2-oxoglutarate metabolism enzyme"
FT                   /id="PRO_0000310720"
FT   REGION          1..41
FT                   /note="2-oxoglutarate dehydrogenase E1, N-terminal part"
FT   REGION          23..145
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          42..107
FT                   /note="Linker"
FT   REGION          108..378
FT                   /note="Succinyltransferase E2"
FT   REGION          379..1269
FT                   /note="2-oxoglutarate dehydrogenase E1, C-terminal part"
FT   COILED          824..855
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        42..60
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        63..77
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        85..121
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        357
FT                   /note="Proton acceptor; for succinyltransferase activity"
FT                   /evidence="ECO:0000250"
FT   BINDING         583
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         622
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         647
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         647
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
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         686
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         686
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         687
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         688
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         719
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         719
FT                   /ligand="thiamine diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58937"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         721
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1061
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1079
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1095
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1130
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1133
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1183
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1190
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT   BINDING         1191
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:A0R2B1"
SQ   SEQUENCE   1269 AA;  140119 MW;  F6F4221B80E76B83 CRC64;
     MSSSPSPFGQ NEWLVEEMYR KFREDPSSVD PSWHEFLVDY NPEPTTDSSA SENGQQTRTA
     APKAPPEPAP APAPKTPDSK TPDSKSQAPK QDSKPQESKP QAKAKPAESK SSTKPADAKS
     EKSGKSGTNG AAKPAAQPAD DSDQNQVLRG AAAAVAKNMS ASLDVPTATS VRAIPAKLMI
     DNRVVINNHL KRTRGGKISF THLIGYAIVA AVKKFPNMNR HFAEVDGKPN AVTPAHTNLG
     LAIDLQGKDG NRQLVVAAIK KADTMRFGQF IAAYEDIVRR ARDGKLTAED FSGVTISLTN
     PGTIGTVHSV PRLMRGQGAI IGVGAMEYPA EFQGASEERI ADLGIGKLIT LTSTYDHRII
     QGAESGDFLR TVHQLLLSDD FFDEIFRELG IPYEPVRWRT DNPDSIEDKN ARVIELIAAY
     RNRGHLMADI DPLRLDSNRF RSHPDLDVLT HGLTLWDLDR EFKVNGFAGA ERKKLRDVLA
     VLRDAYCRHI GVEYTHILEP EQQQWLQERI EGKHEKPTVA QQKYILSRLN AAEAFETFLQ
     TKYVGQKRFS LEGAETVIPA MDAVIDQCAE HALDEVVIGM PHRGRLNVLA NIVGKPYSQI
     FSEFEGNLNP SQAHGSGDVK YHLGSSGTYL QMFGDNDITV SLTANPSHLE AVDPVMEGLV
     RAKQDLLDKG DTEDGYTVVP LMLHGDAAFA GQGVVAETLN LALLRGYRTG GTIHLIVNNQ
     IGFTTSPAAA KSSEYCTDVA KMIGAPIFHV NGDDPEAAVW VSRLAVDFRQ KFKKDVVIDL
     LCYRRRGHNE GDDPSMTQPS MYDVIDTKRG VRKSYTEALI GRGDISMKEA EDALRDYQGQ
     LEQVFNEVRE LEKHEIEPSE SVEADQQIPA KLATAVDKSL LARIGDAHLA VPEGFTVHPR
     VKPVLEKRRE MAYEGKVDWA FAELLALGTM ISEGKLVRLS GQDTRRGTFT QRHSVVIDRK
     TGKEFTPLQL LATDSDGNPT GGKFLVYDSP LSEFAAVGFE YGYSVGNPDA MVLWEAQFGD
     FINGAQSIID EFISSGEAKW GQLSDVVLLL PHGHEGQGPD HTSGRIERFL QLWAEGSMTI
     ALPSTPANYF HLLRRHSLDG IQRPLIVFTP KSMLRNKAAV SDIRDFTEQK FRSVLEEPTY
     TDGDGDRNKV TRILLTSGKI YYELVARKNK ESRDDVAIVR IEQLAPLPKR RLAETLDKYP
     NVEEKFWVQE EPANQGAWPT FGLTLPEMLP DHFTGIKRIS RRAMSAPSSG SSKVHAVEQQ
     EILDEAFAP
//