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A5U1U6 (KGD_MYCTA) Reviewed, UniProtKB/Swiss-Prot

Last modified November 13, 2013. Version 50. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Multifunctional 2-oxoglutarate metabolism enzyme
Alternative name(s):
2-hydroxy-3-oxoadipate synthase
Short name=HOA synthase
Short name=HOAS
EC=2.2.1.5
2-oxoglutarate carboxy-lyase
2-oxoglutarate decarboxylase
Alpha-ketoglutarate decarboxylase
Short name=KG decarboxylase
Short name=KGD
EC=4.1.1.71
Alpha-ketoglutarate-glyoxylate carboligase

Including the following 2 domains:

  1. 2-oxoglutarate dehydrogenase E1 component
    Short name=ODH E1 component
    EC=1.2.4.2
    Alternative name(s):
    Alpha-ketoglutarate dehydrogenase E1 component
    Short name=KDH E1 component
  2. 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 names
Name:kgd
Ordered Locus Names:MRA_1256
OrganismMycobacterium tuberculosis (strain ATCC 25177 / H37Ra) [Complete proteome] [HAMAP]
Taxonomic identifier419947 [NCBI]
Taxonomic lineageBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex

Protein attributes

Sequence length1231 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)

Function

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.

Catalytic activity

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.

Cofactor

Magnesium By similarity.

Thiamine pyrophosphate By similarity.

Enzyme regulation

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

Carbohydrate metabolism; tricarboxylic acid cycle; succinate from 2-oxoglutarate (transferase route): step 1/2.

Carbohydrate metabolism; tricarboxylic acid cycle; succinyl-CoA from 2-oxoglutarate (dehydrogenase route): step 1/1.

Subunit structure

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.

Domain

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 similarities

Belongs to the 2-oxoacid dehydrogenase family. Kgd subfamily.

Sequence caution

The sequence ABQ72996.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12311231Multifunctional 2-oxoglutarate metabolism enzyme
PRO_0000310723

Regions

Region1 – 41412-oxoglutarate dehydrogenase E1, N-terminal part
Region42 – 8847Linker
Region89 – 337249Succinyltransferase E2
Region338 – 12318942-oxoglutarate dehydrogenase E1, C-terminal part
Region541 – 5422Thiamine pyrophosphate binding By similarity
Region606 – 6083Thiamine pyrophosphate binding By similarity
Region649 – 6513Thiamine pyrophosphate binding By similarity
Region1093 – 10964Allosteric activator By similarity
Region1153 – 11542Allosteric activator By similarity
Coiled coil787 – 81731 Potential
Compositional bias61 – 11353Ala-rich

Sites

Active site3161Proton acceptor; for succinyltransferase activity By similarity
Metal binding6491Magnesium By similarity
Metal binding6821Magnesium By similarity
Metal binding6841Magnesium; via carbonyl oxygen By similarity
Binding site58112-oxoglutarate By similarity
Binding site60612-oxoglutarate By similarity
Binding site9561Thiamine pyrophosphate By similarity
Binding site102412-oxoglutarate By similarity
Binding site10421Allosteric activator By similarity
Binding site10581Allosteric activator By similarity
Binding site11461Allosteric activator By similarity

Sequences

Sequence LengthMass (Da)Tools
A5U1U6 [UniParc].

Last modified November 13, 2007. Version 2.
Checksum: 96C255612BA12889

FASTA1,231135,902
        10         20         30         40         50         60 
MANISSPFGQ NEWLVEEMYR KFRDDPSSVD PSWHEFLVDY SPEPTSQPAA EPTRVTSPLV 

        70         80         90        100        110        120 
AERAAAAAPQ APPKPADTAA AGNGVVAALA AKTAVPPPAE GDEVAVLRGA AAAVVKNMSA 

       130        140        150        160        170        180 
SLEVPTATSV RAVPAKLLID NRIVINNQLK RTRGGKISFT HLLGYALVQA VKKFPNMNRH 

       190        200        210        220        230        240 
YTEVDGKPTA VTPAHTNLGL AIDLQGKDGK RSLVVAGIKR CETMRFAQFV TAYEDIVRRA 

       250        260        270        280        290        300 
RDGKLTTEDF AGVTISLTNP GTIGTVHSVP RLMPGQGAII GVGAMEYPAE FQGASEERIA 

       310        320        330        340        350        360 
ELGIGKLITL TSTYDHRIIQ GAESGDFLRT IHELLLSDGF WDEVFRELSI PYLPVRWSTD 

       370        380        390        400        410        420 
NPDSIVDKNA RVMNLIAAYR NRGHLMADTD PLRLDKARFR SHPDLEVLTH GLTLWDLDRV 

       430        440        450        460        470        480 
FKVDGFAGAQ YKKLRDVLGL LRDAYCRHIG VEYAHILDPE QKEWLEQRVE TKHVKPTVAQ 

       490        500        510        520        530        540 
QKYILSKLNA AEAFETFLQT KYVGQKRFSL EGAESVIPMM DAAIDQCAEH GLDEVVIGMP 

       550        560        570        580        590        600 
HRGRLNVLAN IVGKPYSQIF TEFEGNLNPS QAHGSGDVKY HLGATGLYLQ MFGDNDIQVS 

       610        620        630        640        650        660 
LTANPSHLEA VDPVLEGLVR AKQDLLDHGS IDSDGQRAFS VVPLMLHGDA AFAGQGVVAE 

       670        680        690        700        710        720 
TLNLANLPGY RVGGTIHIIV NNQIGFTTAP EYSRSSEYCT DVAKMIGAPI FHVNGDDPEA 

       730        740        750        760        770        780 
CVWVARLAVD FRQRFKKDVV IDMLCYRRRG HNEGDDPSMT NPYVYDVVDT KRGARKSYTE 

       790        800        810        820        830        840 
ALIGRGDISM KEAEDALRDY QGQLERVFNE VRELEKHGVQ PSESVESDQM IPAGLATAVD 

       850        860        870        880        890        900 
KSLLARIGDA FLALPNGFTA HPRVQPVLEK RREMAYEGKI DWAFGELLAL GSLVAEGKLV 

       910        920        930        940        950        960 
RLSGQDSRRG TFSQRHSVLI DRHTGEEFTP LQLLATNSDG SPTGGKFLVY DSPLSEYAAV 

       970        980        990       1000       1010       1020 
GFEYGYTVGN PDAVVLWEAQ FGDFVNGAQS IIDEFISSGE AKWGQLSNVV LLLPHGHEGQ 

      1030       1040       1050       1060       1070       1080 
GPDHTSARIE RFLQLWAEGS MTIAMPSTPS NYFHLLRRHA LDGIQRPLIV FTPKSMLRHK 

      1090       1100       1110       1120       1130       1140 
AAVSEIKDFT EIKFRSVLEE PTYEDGIGDR NKVSRILLTS GKLYYELAAR KAKDNRNDLA 

      1150       1160       1170       1180       1190       1200 
IVRLEQLAPL PRRRLRETLD RYENVKEFFW VQEEPANQGA WPRFGLELPE LLPDKLAGIK 

      1210       1220       1230 
RISRRAMSAP SSGSSKVHAV EQQEILDEAF G 

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References

[1]"Complete genomic sequence of Mycobacterium tuberculosis strain H37Ra, a non-pathogenic variant closely related to the well-characterized pathogenic strain H37Rv."
Wang S.Y., Zheng H.J., Lv L.D., Wang B.F., Zhang X.L., Pu S.Y., Zhu G.F., Wang H.H., Zhao G.P., Zhang Y.
Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 25177 / H37Ra.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CP000611 Genomic DNA. Translation: ABQ72996.1. Different initiation.
RefSeqYP_001282558.1. NC_009525.1.

3D structure databases

ProteinModelPortalA5U1U6.
SMRA5U1U6. Positions 116-335, 367-1231.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING419947.MRA_1256.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaABQ72996; ABQ72996; MRA_1256.
GeneID5214632.
KEGGmra:MRA_1256.
PATRIC18142389. VBIMycTub106795_1401.

Organism-specific databases

CMRSearch...

Phylogenomic databases

eggNOGCOG0508.
HOGENOMHOG000259587.
KOK01616.
OrthoDBEOG6V1M1F.
ProtClustDBPRK12270.

Enzyme and pathway databases

BioCycMTUB419947:GJ8N-1295-MONOMER.
UniPathwayUPA00223; UER00997.
UPA00223; UER01001.

Family and domain databases

Gene3D3.30.559.10. 1 hit.
InterProIPR001078. 2-oxoacid_DH_actylTfrase.
IPR011603. 2oxoglutarate_DH_E1.
IPR023213. CAT-like_dom.
IPR001017. DH_E1.
IPR005475. Transketolase-like_Pyr-bd.
[Graphical view]
PANTHERPTHR23152. PTHR23152. 1 hit.
PfamPF00198. 2-oxoacid_dh. 1 hit.
PF00676. E1_dh. 1 hit.
PF02779. Transket_pyr. 1 hit.
[Graphical view]
PIRSFPIRSF000157. Oxoglu_dh_E1. 1 hit.
SMARTSM00861. Transket_pyr. 1 hit.
[Graphical view]
TIGRFAMsTIGR00239. 2oxo_dh_E1. 1 hit.
ProtoNetSearch...

Entry information

Entry nameKGD_MYCTA
AccessionPrimary (citable) accession number: A5U1U6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: November 13, 2013
This is version 50 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways