KGD_MYCUA
ID KGD_MYCUA Reviewed; 1238 AA.
AC A0PVU7;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 93.
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=MUL_4500;
OS Mycobacterium ulcerans (strain Agy99).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=362242;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Agy99;
RX PubMed=17210928; DOI=10.1101/gr.5942807;
RA Stinear T.P., Seemann T., Pidot S., Frigui W., Reysset G., Garnier T.,
RA Meurice G., Simon D., Bouchier C., Ma L., Tichit M., Porter J.L., Ryan J.,
RA Johnson P.D.R., Davies J.K., Jenkin G.A., Small P.L.C., Jones L.M.,
RA Tekaia F., Laval F., Daffe M., Parkhill J., Cole S.T.;
RT "Reductive evolution and niche adaptation inferred from the genome of
RT Mycobacterium ulcerans, the causative agent of Buruli ulcer.";
RL Genome Res. 17:192-200(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=(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}.
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DR EMBL; CP000325; ABL06466.1; -; Genomic_DNA.
DR RefSeq; WP_011742065.1; NC_008611.1.
DR AlphaFoldDB; A0PVU7; -.
DR SMR; A0PVU7; -.
DR STRING; 362242.MUL_4500; -.
DR PRIDE; A0PVU7; -.
DR EnsemblBacteria; ABL06466; ABL06466; MUL_4500.
DR KEGG; mul:MUL_4500; -.
DR eggNOG; COG0508; Bacteria.
DR eggNOG; COG0567; Bacteria.
DR HOGENOM; CLU_004709_1_0_11; -.
DR OMA; RDSYCRT; -.
DR UniPathway; UPA00223; UER00997.
DR UniPathway; UPA00223; UER01001.
DR Proteomes; UP000000765; 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 Thiamine pyrophosphate; Transferase; Tricarboxylic acid cycle.
FT CHAIN 1..1238
FT /note="Multifunctional 2-oxoglutarate metabolism enzyme"
FT /id="PRO_0000310724"
FT REGION 1..41
FT /note="2-oxoglutarate dehydrogenase E1, N-terminal part"
FT REGION 40..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..94
FT /note="Linker"
FT REGION 95..343
FT /note="Succinyltransferase E2"
FT REGION 344..1238
FT /note="2-oxoglutarate dehydrogenase E1, C-terminal part"
FT REGION 1100..1103
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT REGION 1160..1161
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT COILED 794..824
FT /evidence="ECO:0000255"
FT COMPBIAS 58..74
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 322
FT /note="Proton acceptor; for succinyltransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 548..549
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 588
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 613..615
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 613
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 656..658
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 656
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 689
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 691
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 963
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 1031
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 1049
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT BINDING 1065
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"
SQ SEQUENCE 1238 AA; 136742 MW; B9A7DB3108194D2A CRC64;
MANISSPFGQ NEWLVEEMYR KFRDDPSSVD PSWHEFLVDY NPESTQEATE PAVVKPAAAP
AKPAPAPAPA KPAAGPPAAG NGSPAAAPSA KPAAAPAKAP APPPAEGDEM QVLRGAAAAV
VKNMSASLDV PTATSVRAVP AKLLIDNRIV INNQLKRNRG GKISFTHLLG YALVQAVKKF
PNMNRHYLDV DGKPNAVTPA HTNLGLAIDL QGKDGKRALV VAGIKRCETM RFAQFVTAYE
DIVRRARDGK LTAEDFSGVT ISLTNPGTIG TVHSVPRLMA GQGAIIGVGA MEYPAEFQGA
SEERIAELGI GKLITLTSTY DHRIIQGAES GDFLRTIHQM LLADEFWDEI FRELSIPYLP
VRWRPDNPDS IVDKNARIIE LIAAYRNRGH LMADIDPLRL DKTRFRSHPD LDVCTHGLTL
WDLDRSFKVG GCFAGPQNMK LRDVLSILRD TYCRHVGVEY THILEPEQQQ WLQQRVEAKH
VKPTVAQQKY VLSKLNAAEA FETFLQTKYV GQKRFSLEGA ESVIPMMDAA IDQCAEYGLD
EVVIGMPHRG RLNVLANIVG KPYSQIFSEF EGNLNPSQAH GSGDVKYHLG ATGVYLQMFG
DNDIQVSLTA NPSHLEAVDP VLEGLVRAKQ DLLEHGETDT ENQRAFSVVP MMLHGDAAFA
GQGVVAETLN LANLPGYRVG GTIHIIVNNQ IGFTTAPEYS RSTEYCTDVA KTIGAPIFHV
NGDDPEACVW VARLAVDFRQ RFNKDVIIDM LCYRRRGHNE GDDPSMTNPR MYDVVDTKRG
VRKSYTEALI GRGDISIKEA EDALRDYQGQ LEQVFNEVRE LEKHGAQPSE SVESDQMIPA
GLATAVDKSL LARIGDAFLA VPDGFTTHPR VQPVLEKRRE MAYEGKIDWA FAELLALGSL
VAEGKLVRFS GQDTRRGTFS QRHSVIIDRH TREEFTPLQL LTTNKDGSPT GGKFLVYDSP
LSEYAAVGFE YGYTVGNPDA VVLWEAQFGD FVNGAQSIID EFISSGEAKW GQLSNVVLLL
PHGHEGQGPD HTSGRIERFL QLWAEGSMTI AMPSTPSNYF HLLRRHALDG IQRPLIVFTP
KSMLRNKAAV SDIKDFTEIK FRSVLEEPTY EDGVGDRNLV NRILLTSGKI YYEMVARKAK
DKREDVAIVR VEQLAPLPRR RLRETLDRYP NAKEFFWVQE EPANQGAWPR FGLELPELLP
EKLSGVKRIS RRAMSAPSSG SSKVHAVEQQ EILDTAFG
