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A0R2B1 (KGD_MYCS2) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 62. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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
Synonyms:sucA
Ordered Locus Names:MSMEG_5049, MSMEI_4922
OrganismMycobacterium smegmatis (strain ATCC 700084 / mc(2)155) [Reference proteome] [HAMAP]
Taxonomic identifier246196 [NCBI]
Taxonomic lineageBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacterium

Protein attributes

Sequence length1227 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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. Ref.4 Ref.5

Catalytic activity

2-oxoglutarate + glyoxylate = 2-hydroxy-3-oxoadipate + CO2. Ref.5

2-oxoglutarate = succinate semialdehyde + CO2. Ref.5

2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2. Ref.5

Succinyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-succinyldihydrolipoyl)lysine. Ref.5

Cofactor

Magnesium. Ref.5

Thiamine pyrophosphate. Ref.5

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. Both the phosphoadenosine and acetyl moieties of acetyl-CoA are important for activation because neither CoA nor the synthetic compound S-(2-acetamidoethyl)-ethanethioate (which mimics the terminal acetyl-phosphopantetheine group of acetyl-CoA) has an activation effect. Ref.4 Ref.5

Pathway

Carbohydrate metabolism; tricarboxylic acid cycle; succinate from 2-oxoglutarate (transferase route): step 1/2. Ref.5

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

Subunit structure

Homodimer. Interacts with the FHA domain of unphosphorylated GarA. The 2-oxoglutarate dehydrogenase (ODH) complex contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3). Ref.4 Ref.5

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.

Disruption phenotype

Cells lacking this gene do not show any ODH activity, in contrast to wild-type, demonstrating that this protein is part of a functional ODH complex in mycobacteria. Ref.5

Sequence similarities

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

Biophysicochemical properties

Kinetic parameters:

KM=0.54 mM for alpha-ketoglutarate Ref.4

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12271227Multifunctional 2-oxoglutarate metabolism enzyme
PRO_0000310718

Regions

Region1 – 41412-oxoglutarate dehydrogenase E1, N-terminal part
Region42 – 8847Linker
Region89 – 335247Succinyltransferase E2
Region336 – 12278922-oxoglutarate dehydrogenase E1, C-terminal part
Region539 – 5402Thiamine pyrophosphate binding
Region604 – 6063Thiamine pyrophosphate binding
Region645 – 6473Thiamine pyrophosphate binding
Region1089 – 10924Allosteric activator
Region1149 – 11502Allosteric activator
Coiled coil783 – 81432 Potential

Sites

Active site3141Proton acceptor; for succinyltransferase activity By similarity
Metal binding6451Magnesium
Metal binding6781Magnesium
Metal binding6801Magnesium; via carbonyl oxygen
Binding site57912-oxoglutarate
Binding site60412-oxoglutarate
Binding site9521Thiamine pyrophosphate
Binding site102012-oxoglutarate
Binding site10381Allosteric activator
Binding site10541Allosteric activator
Binding site11421Allosteric activator

Experimental info

Mutagenesis5391H → A: Loss of KG decarboxylase activity. Ref.5
Mutagenesis5791H → A: Loss of KG decarboxylase activity. Ref.5
Mutagenesis7471H → A: 40-fold decrease in KG decarboxylase activity. Ref.5
Mutagenesis7811R → A: Increase in KG decarboxylase activity. Ref.5
Mutagenesis10201H → A: Loss of KG decarboxylase activity. Ref.5
Mutagenesis10341E → A: Loss of activation by acetyl-CoA. Ref.5
Mutagenesis10621R → A: Loss of activation by acetyl-CoA. Ref.5

Secondary structure

................................................................................................................................................................................................ 1227
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
A0R2B1 [UniParc].

Last modified January 9, 2007. Version 1.
Checksum: 76C5BFFD1638A391

FASTA1,227135,944
        10         20         30         40         50         60 
MSSSPSPFGQ NEWLVEEMYR KFRDDPSSVD PSWHEFLVDY SPEPTTDSAS NGRTTTAAPV 

        70         80         90        100        110        120 
TPPTPAPAPA PEPKAAPKPA AKTEAKPAKP AKSATPAKGD ESQILRGAAA AVVKNMNASL 

       130        140        150        160        170        180 
EVPTATSVRA IPAKLMIDNR VVINNHLKRT RGGKISFTHL LGYAIVQAVK KFPNMNRHFA 

       190        200        210        220        230        240 
VVDGKPTAIT PAHTNLGLAI DLQGKDGNRS LVVAAIKRCE TMRFGQFIAA YEDIVRRARD 

       250        260        270        280        290        300 
GKLTAEDFSG VTISLTNPGT LGTVHSVPRL MQGQGAIIGA GAMEYPAEFQ GASEERIADL 

       310        320        330        340        350        360 
GIGKLITLTS TYDHRIIQGA ESGDFLRTIH QLLLDDDFFD EIFRELGIPY EPVRWRTDNP 

       370        380        390        400        410        420 
DSIEDKNARV IELIAAYRNR GHLMADIDPL RLDNTRFRSH PDLDVNSHGL TLWDLDREFK 

       430        440        450        460        470        480 
VDGFAGVQRK KLRDILSVLR DAYCRHVGVE YTHILEPEQQ RWIQERVETK HDKPTVAEQK 

       490        500        510        520        530        540 
YILSKLNAAE AFETFLQTKY VGQKRFSLEG AETVIPMMDA VIDQCAEHGL DEVVIAMPHR 

       550        560        570        580        590        600 
GRLNVLANIV GKPYSQIFSE FEGNLNPSQA HGSGDVKYHL GATGTYIQMF GDNDIEVSLT 

       610        620        630        640        650        660 
ANPSHLEAVD PVLEGLVRAK QDLLDTGEEG SDNRFSVVPL MLHGDAAFAG QGVVAETLNL 

       670        680        690        700        710        720 
ALLRGYRTGG TIHIVVNNQI GFTTAPTDSR SSEYCTDVAK MIGAPIFHVN GDDPEACAWV 

       730        740        750        760        770        780 
ARLAVDFRQA FKKDVVIDML CYRRRGHNEG DDPSMTQPYM YDVIDTKRGS RKAYTEALIG 

       790        800        810        820        830        840 
RGDISMKEAE DALRDYQGQL ERVFNEVREL EKHEIEPSES VEADQQIPSK LATAVDKAML 

       850        860        870        880        890        900 
QRIGDAHLAL PEGFTVHPRV RPVLEKRREM AYEGRIDWAF AELLALGSLI AEGKLVRLSG 

       910        920        930        940        950        960 
QDTQRGTFTQ RHAVIVDRKT GEEFTPLQLL ATNPDGTPTG GKFLVYNSAL SEFAAVGFEY 

       970        980        990       1000       1010       1020 
GYSVGNPDAM VLWEAQFGDF VNGAQSIIDE FISSGEAKWG QLSDVVLLLP HGHEGQGPDH 

      1030       1040       1050       1060       1070       1080 
TSGRIERFLQ LWAEGSMTIA MPSTPANYFH LLRRHGKDGI QRPLIVFTPK SMLRNKAAVS 

      1090       1100       1110       1120       1130       1140 
DIRDFTESKF RSVLEEPMYT DGEGDRNKVT RLLLTSGKIY YELAARKAKE NREDVAIVRI 

      1150       1160       1170       1180       1190       1200 
EQLAPLPRRR LAETLDRYPN VKEKFWVQEE PANQGAWPSF GLTLPEILPD HFTGLKRISR 

      1210       1220 
RAMSAPSSGS SKVHAVEQQE ILDTAFG 

« Hide

References

« Hide 'large scale' references
[1]Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C., Fraser C.M.
Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 700084 / mc(2)155.
[2]"Interrupted coding sequences in Mycobacterium smegmatis: authentic mutations or sequencing errors?"
Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C., Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.
Genome Biol. 8:R20.1-R20.9(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 700084 / mc(2)155.
[3]"Ortho-proteogenomics: multiple proteomes investigation through orthology and a new MS-based protocol."
Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M., Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.
Genome Res. 19:128-135(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Strain: ATCC 700084 / mc(2)155.
[4]"Regulation of glutamate metabolism by protein kinases in mycobacteria."
O'Hare H.M., Duran R., Cervenansky C., Bellinzoni M., Wehenkel A.M., Pritsch O., Obal G., Baumgartner J., Vialaret J., Johnsson K., Alzari P.M.
Mol. Microbiol. 70:1408-1423(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN 2-OXOGLUTARATE DECARBOXYLATION, ENZYME REGULATION, KINETIC PARAMETERS, INTERACTION WITH GARA.
Strain: ATCC 700084 / mc(2)155.
[5]"Functional plasticity and allosteric regulation of alpha-ketoglutarate decarboxylase in central mycobacterial metabolism."
Wagner T., Bellinzoni M., Wehenkel A., O'Hare H.M., Alzari P.M.
Chem. Biol. 18:1011-1020(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 116-1227 IN COMPLEXES WITH THIAMINE PYROPHOSPHATE; ACETYL-COA; ENAMINE-THDP REACTION INTERMEDIATE AND MAGNESIUM, FUNCTION AS A MULTIFUNCTIONAL ENZYME, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, SUBUNIT, PATHWAY, MUTAGENESIS OF HIS-539; HIS-579; HIS-747; ARG-781; HIS-1020; GLU-1034 AND ARG-1062, DISRUPTION PHENOTYPE.
Strain: ATCC 700084 / mc(2)155.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CP000480 Genomic DNA. Translation: ABK74238.1.
CP001663 Genomic DNA. Translation: AFP41366.1.
RefSeqYP_006569661.1. NC_018289.1.
YP_889299.1. NC_008596.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XT6X-ray2.74A/B116-1227[»]
2XT9X-ray2.20A361-1227[»]
2XTAX-ray2.20A/B/C/D361-1227[»]
2Y0PX-ray2.40A/B/C/D361-1227[»]
2YICX-ray1.96A/B/C/D361-1227[»]
2YIDX-ray2.25A/B/C/D361-1227[»]
3ZHQX-ray2.50A/B/C/D361-1227[»]
3ZHRX-ray2.10A/B/C/D361-1227[»]
3ZHSX-ray2.10A/B/C/D361-1227[»]
3ZHTX-ray2.15A/B/C/D361-1227[»]
3ZHUX-ray2.30A/B/C/D361-1227[»]
3ZHVX-ray2.30A/B/C/D361-1227[»]
ProteinModelPortalA0R2B1.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActA0R2B1. 1 interaction.
STRING246196.MSMEG_5049.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaABK74238; ABK74238; MSMEG_5049.
AFP41366; AFP41366; MSMEI_4922.
GeneID13430142.
4535402.
KEGGmsg:MSMEI_4922.
msm:MSMEG_5049.
PATRIC18082397. VBIMycSme59918_4927.

Phylogenomic databases

eggNOGCOG0508.
HOGENOMHOG000259587.
KOK01616.
OMAHILRRQL.
OrthoDBEOG6V1M1F.
ProtClustDBPRK12270.

Enzyme and pathway databases

BioCycMSME246196:GJ4Y-5048-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...

Other

EvolutionaryTraceA0R2B1.

Entry information

Entry nameKGD_MYCS2
AccessionPrimary (citable) accession number: A0R2B1
Secondary accession number(s): I7GDF5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: January 9, 2007
Last modified: March 19, 2014
This is version 62 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways