KGD_MYCSJ
ID KGD_MYCSJ Reviewed; 1264 AA.
AC A3Q3N5;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 92.
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=Mjls_3987;
OS Mycobacterium sp. (strain JLS).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; unclassified Mycobacterium.
OX NCBI_TaxID=164757;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JLS;
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 Chain P., Malfatti S., Shin M., Vergez L., Schmutz J., Larimer F., Land M.,
RA Hauser L., Kyrpides N., Mikhailova N., Miller C.D., Anderson A.J.,
RA Sims R.C., Richardson P.;
RT "Complete sequence of Mycobacterium sp. JLS.";
RL Submitted (FEB-2007) 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; CP000580; ABN99762.1; -; Genomic_DNA.
DR AlphaFoldDB; A3Q3N5; -.
DR SMR; A3Q3N5; -.
DR STRING; 164757.Mjls_3987; -.
DR PRIDE; A3Q3N5; -.
DR KEGG; mjl:Mjls_3987; -.
DR HOGENOM; CLU_004709_1_0_11; -.
DR OMA; RDSYCRT; -.
DR BioCyc; MSP164757:G1G8C-4028-MON; -.
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..1264
FT /note="Multifunctional 2-oxoglutarate metabolism enzyme"
FT /id="PRO_0000310719"
FT REGION 1..41
FT /note="2-oxoglutarate dehydrogenase E1, N-terminal part"
FT REGION 23..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..102
FT /note="Linker"
FT REGION 103..373
FT /note="Succinyltransferase E2"
FT REGION 374..1264
FT /note="2-oxoglutarate dehydrogenase E1, C-terminal part"
FT REGION 1125..1128
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT REGION 1185..1186
FT /note="Acetyl-CoA; allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT COILED 819..850
FT /evidence="ECO:0000255"
FT COMPBIAS 42..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..116
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 352
FT /note="Proton acceptor; for succinyltransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 577..578
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 617
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 642..644
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 642
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 681..683
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 681
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 714
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 716
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 988
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 1056
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 1074
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT BINDING 1090
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
FT BINDING 1178
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:A0R2B1"
SQ SEQUENCE 1264 AA; 139593 MW; C5068956C2130DAC CRC64;
MSSSPSPFGQ NEWLVEEMYR KFREDPSSVD PSWHEFLVDY NPEPTTDSSA SENGQQTRTA
APKAPPEPAP APAPKSQDSK SQAPKQDSKP QESKPQAKAK PAESKSSTKP ADAKSEKSGK
SGTNGAAKPA AQPADDSDQN QVLRGAAAAV AKNMSASLDV PTATSVRAIP AKLMIDNRVV
INNHLKRTRG GKISFTHLIG YAIVAAVKKF PNMNRHFAEV DGKPNAVTPA HTNLGLAIDL
QGKDGNRQLV VAAIKKADTM RFGQFIAAYE DIVRRARDGK LTAEDFSGVT ISLTNPGTIG
TVHSVPRLMR GQGAIIGVGA MEYPAEFQGA SEERIADLGI GKLITLTSTY DHRIIQGAES
GDFLRTVHQL LLSDDFFDEI FRELGIPYEP VRWRTDNPDS IEDKNARVIE LIAAYRNRGH
LMADIDPLRL DSNRFRSHPD LDVLTHGLTL WDLDREFKVN GFAGAERKKL RDVLAVLRDA
YCRHIGVEYT HILEPEQQQW LQERIEGKHE KPTVAQQKYI LSRLNAAEAF ETFLQTKYVG
QKRFSLEGAE TVIPAMDAVI DQCAEHALDE VVIGMPHRGR LNVLANIVGK PYSQIFSEFE
GNLNPSQAHG SGDVKYHLGS SGTYLQMFGD NDITVSLTAN PSHLEAVDPV MEGLVRAKQD
LLDKGDTEDG YTVVPLMLHG DAAFAGQGVV AETLNLALLR GYRTGGTIHL IVNNQIGFTT
SPAAAKSSEY CTDVAKMIGA PIFHVNGDDP EAAVWVSRLA VDFRQKFKKD VVIDLLCYRR
RGHNEGDDPS MTQPSMYDVI DTKRGVRKSY TEALIGRGDI SMKEAEDALR DYQGQLEQVF
NEVRELEKHE IEPSESVEAD QQIPAKLATA VDKSLLARIG DAHLAVPEGF TVHPRVKPVL
EKRREMAYEG KVDWAFAELL ALGTMISEGK LVRLSGQDTR RGTFTQRHSV VIDRKTGKEF
TPLQLLATDS DGNPTGGKFL VYDSPLSEFA AVGFEYGYSV GNPDAMVLWE AQFGDFINGA
QSIIDEFISS GEAKWGQLSD VVLLLPHGHE GQGPDHTSGR IERFLQLWAE GSMTIALPST
PANYFHLLRR HSLDGIQRPL IVFTPKSMLR NKAAVSDIRD FTEQKFRSVL EEPTYTDGDG
DRNKVTRILL TSGKIYYELV ARKNKESRDD VAIVRIEQLA PLPKRRLAET LDKYPNVDEK
FWVQEEPANQ GAWPTFGLTL PEMLPDHFTG IKRISRRAMS APSSGSSKVH AVEQQEILDE
AFAP
