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Protein

Multifunctional 2-oxoglutarate metabolism enzyme

Gene

kgd

Organism
Mycobacterium leprae (strain TN)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

Shows three enzymatic activities that share a first common step, the attack of thiamine-PP on 2-oxoglutarate (alpha-ketoglutarate, KG), leading to the formation of an enamine-thiamine-PP intermediate upon decarboxylation. Thus, displays KGD activity, catalyzing the decarboxylation from five-carbon 2-oxoglutarate to four-carbon succinate semialdehyde (SSA). Also catalyzes C-C bond formation between the activated aldehyde formed after decarboxylation of alpha-ketoglutarate and the carbonyl of glyoxylate (GLX), to yield 2-hydroxy-3-oxoadipate (HOA), which spontaneously decarboxylates to form 5-hydroxylevulinate (HLA). And is also a component of the 2-oxoglutarate dehydrogenase (ODH) complex, that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO2. The KG decarboxylase and KG dehydrogenase reactions provide two alternative, tightly regulated, pathways connecting the oxidative and reductive branches of the TCA cycle (By similarity).By similarity

Catalytic activityi

2-oxoglutarate + glyoxylate = 2-hydroxy-3-oxoadipate + CO2.
2-oxoglutarate = succinate semialdehyde + CO2.
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2.
Succinyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-succinyldihydrolipoyl)lysine.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Alpha-ketoglutarate dehydrogenase and decarboxylase activities are inhibited by unphosphorylated GarA, and allosterically activated by acetyl-CoA, the main substrate of the TCA cycle.By similarity

Pathway: tricarboxylic acid cycle

This protein is involved in step 1 of the subpathway that synthesizes succinate from 2-oxoglutarate (transferase route).
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Multifunctional 2-oxoglutarate metabolism enzyme (kgd)
  2. no protein annotated in this organism
This subpathway is part of the pathway tricarboxylic acid cycle, which is itself part of Carbohydrate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes succinate from 2-oxoglutarate (transferase route), the pathway tricarboxylic acid cycle and in Carbohydrate metabolism.

Pathway: tricarboxylic acid cycle

This protein is involved in step 1 of the subpathway that synthesizes succinyl-CoA from 2-oxoglutarate (dehydrogenase route).
Proteins known to be involved in this subpathway in this organism are:
  1. Multifunctional 2-oxoglutarate metabolism enzyme (kgd)
This subpathway is part of the pathway tricarboxylic acid cycle, which is itself part of Carbohydrate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes succinyl-CoA from 2-oxoglutarate (dehydrogenase route), the pathway tricarboxylic acid cycle and in Carbohydrate metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei325 – 3251Proton acceptor; for succinyltransferase activityBy similarity
Binding sitei590 – 59012-oxoglutarateBy similarity
Binding sitei615 – 61512-oxoglutarateBy similarity
Metal bindingi657 – 6571MagnesiumBy similarity
Metal bindingi690 – 6901MagnesiumBy similarity
Metal bindingi692 – 6921Magnesium; via carbonyl oxygenBy similarity
Binding sitei964 – 9641Thiamine pyrophosphateBy similarity
Binding sitei1032 – 103212-oxoglutarateBy similarity
Binding sitei1050 – 10501Allosteric activatorBy similarity
Binding sitei1066 – 10661Allosteric activatorBy similarity
Binding sitei1154 – 11541Allosteric activatorBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Decarboxylase, Lyase, Oxidoreductase, Transferase

Keywords - Biological processi

Tricarboxylic acid cycle

Keywords - Ligandi

Magnesium, Metal-binding, Thiamine pyrophosphate

Enzyme and pathway databases

UniPathwayiUPA00223; UER00997.
UPA00223; UER01001.

Names & Taxonomyi

Protein namesi
Recommended name:
Multifunctional 2-oxoglutarate metabolism enzyme
Alternative name(s):
2-hydroxy-3-oxoadipate synthase (EC:2.2.1.5)
Short name:
HOA synthase
Short name:
HOAS
2-oxoglutarate carboxy-lyase
2-oxoglutarate decarboxylase
Alpha-ketoglutarate decarboxylase (EC:4.1.1.71)
Short name:
KG decarboxylase
Short name:
KGD
Alpha-ketoglutarate-glyoxylate carboligase
Including the following 2 domains:
2-oxoglutarate dehydrogenase E1 component (EC:1.2.4.2)
Short name:
ODH E1 component
Alternative name(s):
Alpha-ketoglutarate dehydrogenase E1 component
Short name:
KDH E1 component
Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (EC:2.3.1.61)
Alternative name(s):
2-oxoglutarate dehydrogenase complex E2 component
Short name:
ODH E2 component
Short name:
OGDC-E2
Dihydrolipoamide succinyltransferase
Gene namesi
Name:kgd
Ordered Locus Names:ML1095
OrganismiMycobacterium leprae (strain TN)
Taxonomic identifieri272631 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacterium
ProteomesiUP000000806 Componenti: Chromosome

Organism-specific databases

LepromaiML1095.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12381238Multifunctional 2-oxoglutarate metabolism enzymePRO_0000310716Add
BLAST

Interactioni

Subunit structurei

Homodimer. The 2-oxoglutarate dehydrogenase (ODH) complex contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) (By similarity).By similarity

Protein-protein interaction databases

STRINGi272631.ML1095.

Structurei

3D structure databases

ProteinModelPortaliQ9CC97.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 41412-oxoglutarate dehydrogenase E1, N-terminal partAdd
BLAST
Regioni42 – 9756LinkerAdd
BLAST
Regioni98 – 346249Succinyltransferase E2Add
BLAST
Regioni347 – 12388922-oxoglutarate dehydrogenase E1, C-terminal partAdd
BLAST
Regioni550 – 5512Thiamine pyrophosphate bindingBy similarity
Regioni615 – 6173Thiamine pyrophosphate bindingBy similarity
Regioni657 – 6593Thiamine pyrophosphate bindingBy similarity
Regioni1101 – 11044Allosteric activatorBy similarity
Regioni1161 – 11622Allosteric activatorBy similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili795 – 82531Sequence AnalysisAdd
BLAST

Domaini

Is a fusion protein with two major domains exhibiting structural features of an E1 and E2 protein, and a short sequence stretch of E1 localized at the N-terminus, which is connected by a linker region to the rest of the protein.By similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0508.
HOGENOMiHOG000259587.
KOiK01616.
OrthoDBiEOG6V1M1F.

Family and domain databases

Gene3Di3.30.559.10. 1 hit.
3.40.50.970. 2 hits.
InterProiIPR001078. 2-oxoacid_DH_actylTfrase.
IPR011603. 2oxoglutarate_DH_E1.
IPR023213. CAT-like_dom.
IPR001017. DH_E1.
IPR029061. THDP-binding.
IPR005475. Transketolase-like_Pyr-bd.
[Graphical view]
PANTHERiPTHR23152. PTHR23152. 1 hit.
PfamiPF00198. 2-oxoacid_dh. 1 hit.
PF00676. E1_dh. 1 hit.
PF02779. Transket_pyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000157. Oxoglu_dh_E1. 1 hit.
SMARTiSM00861. Transket_pyr. 1 hit.
[Graphical view]
SUPFAMiSSF52518. SSF52518. 2 hits.
TIGRFAMsiTIGR00239. 2oxo_dh_E1. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9CC97-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANISSPFGQ NEWLVEEMYR KFRDDPSSVD PSWHEFLVDY NPESTAEPVL
60 70 80 90 100
TDPTSTDKQP SATPQAKPAA AADPVASRAK PATTPTVANG TAAGSAAAPA
110 120 130 140 150
KTTTTPPIEG DELQVLRGAA AVVVKNMSAS LDVPTATSVR AVPAKLMIDN
160 170 180 190 200
RTVINNQLKR NRGGKISFTH LLGYALVQAV KKFPNINRHY AEIDGKPIAV
210 220 230 240 250
TPAHTNLGLA IDLQGKDGKR SLVVAGIKRC EELRFAQFVT AYEDIVRRAR
260 270 280 290 300
DGKLTAEDFA GVTISLTNPG TIGTVHSVPR LMTGQGAIIG VGAMEYPAEF
310 320 330 340 350
QGASAERIAE LGIGKLITLT STYDHRIIQG AESGDFLRTI HEMVLSDSFW
360 370 380 390 400
DEIFRELSIP YLPVRWRTDN PDSIVDKNAR VMELIAAYRN RGHLMADIDP
410 420 430 440 450
LRLDNTRFRS HPDLDLLTHG LTLWDLDRVF KVNGFGGWKY KKLRDVLGLL
460 470 480 490 500
RDAYCRHIGV EYTHILDPEQ QEWLQQRVET KNVKPTVAEQ KYILSKLNAA
510 520 530 540 550
EAFETFLHTK YVGQKRFSLE GAESVIPMMD AAIDQCAKHG LDEVVIGMPH
560 570 580 590 600
RGRLNVLANI VGKPYSQIFT EFEGNLNPTL AHSSGDVKYH LGATGLYLQM
610 620 630 640 650
FGDNDIQVSL TANPSHLEAV DPVLEGLVRA KQDLLNKDTN GNQDEAFSVV
660 670 680 690 700
PMMLHGDAAF AGQGVVAETL NLANLPGYRV GGTIHIIVNN QIGFTTAPEY
710 720 730 740 750
SRSSEYCTDV AKMIGAPIFH VNGDDPEACV WVAKLAVDFR QRFKKDVVID
760 770 780 790 800
MLCYRRRGHN EGDDPSMTNP YMYDVVDTKR GARKSYTEAL IGRGDISLKE
810 820 830 840 850
AEDALRDYQG QLERVFNEVR DLEKHGVQPS ESVESDQMIP AGLSTAVDKA
860 870 880 890 900
LLARIGDAFL AVPEGFTVHP RVQPVLEKRR EMAYEGKIDW AFAELLALGS
910 920 930 940 950
LVAEGKLVRL SGQDTKRGTF SQRHSVIIDR HTGEEFTPLQ LLANNPDGSP
960 970 980 990 1000
TGGKFLVYNS PLSEYAAVGF EYGYTVGNPD AVVLWEAQFG DFVNGAQSII
1010 1020 1030 1040 1050
DEFINSGEAK WGQLSTVVLL LPHGHEGQGP DHTSGRIERF LQLWAEGSMT
1060 1070 1080 1090 1100
FAVPSTPSNY FHLLRRHALD GIKRPLIVFT PKSMLRNKAA VSDIKDFTEI
1110 1120 1130 1140 1150
KFRSVLEEPT YEDSIDDRSK VTRVLLTCGK LYYELAARKI KDNRDDVAIV
1160 1170 1180 1190 1200
RIEQLAPLPR RRLGETLDRY ENAKEFFWVQ EEPANQGAWP RFGLELPELL
1210 1220 1230
PRLTGIKRIS RRAMSAPSSG SSKVHAVEQQ EILDTAFG
Length:1,238
Mass (Da):137,020
Last modified:November 13, 2007 - v2
Checksum:i62B154E8A1D9A0E8
GO

Sequence cautioni

The sequence CAC31476.1 differs from that shown. Reason: Erroneous initiation. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL583920 Genomic DNA. Translation: CAC31476.1. Different initiation.
PIRiA87046.
RefSeqiNP_301802.2. NC_002677.1.
WP_010908126.1. NC_002677.1.

Genome annotation databases

EnsemblBacteriaiCAC31476; CAC31476; CAC31476.
GeneIDi910185.
KEGGimle:ML1095.
PATRICi18054027. VBIMycLep78757_1959.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL583920 Genomic DNA. Translation: CAC31476.1. Different initiation.
PIRiA87046.
RefSeqiNP_301802.2. NC_002677.1.
WP_010908126.1. NC_002677.1.

3D structure databases

ProteinModelPortaliQ9CC97.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi272631.ML1095.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCAC31476; CAC31476; CAC31476.
GeneIDi910185.
KEGGimle:ML1095.
PATRICi18054027. VBIMycLep78757_1959.

Organism-specific databases

LepromaiML1095.

Phylogenomic databases

eggNOGiCOG0508.
HOGENOMiHOG000259587.
KOiK01616.
OrthoDBiEOG6V1M1F.

Enzyme and pathway databases

UniPathwayiUPA00223; UER00997.
UPA00223; UER01001.

Family and domain databases

Gene3Di3.30.559.10. 1 hit.
3.40.50.970. 2 hits.
InterProiIPR001078. 2-oxoacid_DH_actylTfrase.
IPR011603. 2oxoglutarate_DH_E1.
IPR023213. CAT-like_dom.
IPR001017. DH_E1.
IPR029061. THDP-binding.
IPR005475. Transketolase-like_Pyr-bd.
[Graphical view]
PANTHERiPTHR23152. PTHR23152. 1 hit.
PfamiPF00198. 2-oxoacid_dh. 1 hit.
PF00676. E1_dh. 1 hit.
PF02779. Transket_pyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000157. Oxoglu_dh_E1. 1 hit.
SMARTiSM00861. Transket_pyr. 1 hit.
[Graphical view]
SUPFAMiSSF52518. SSF52518. 2 hits.
TIGRFAMsiTIGR00239. 2oxo_dh_E1. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: TN.

Entry informationi

Entry nameiKGD_MYCLE
AccessioniPrimary (citable) accession number: Q9CC97
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: June 24, 2015
This is version 85 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.