KGD_MYCSK
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 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=Mkms_4047;
OS Mycobacterium sp. (strain KMS).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; unclassified 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=(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; CP000518; ABL93239.1; -; Genomic_DNA.
DR RefSeq; WP_011561352.1; NC_008705.1.
DR AlphaFoldDB; A1UK81; -.
DR SMR; A1UK81; -.
DR STRING; 189918.Mkms_4047; -.
DR EnsemblBacteria; ABL93239; ABL93239; Mkms_4047.
DR KEGG; mkm:Mkms_4047; -.
DR HOGENOM; CLU_004709_1_0_11; -.
DR OMA; RDSYCRT; -.
DR OrthoDB; 29166at2; -.
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 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..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 REGION 1130..1133
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT REGION 1190..1191
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
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 582..583
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 622
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 647..649
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 647
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 686..688
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 686
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 719
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 721
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 993
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 1061
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
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 1183
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
