D2HDH_PSEU5
ID D2HDH_PSEU5 Reviewed; 464 AA.
AC A4VGK4;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=D-2-hydroxyglutarate dehydrogenase {ECO:0000303|PubMed:28827360, ECO:0000303|PubMed:30131334};
DE Short=D-2-HG dehydrogenase {ECO:0000303|PubMed:28827360, ECO:0000303|PubMed:30131334};
DE Short=D2HGDH {ECO:0000303|PubMed:28827360, ECO:0000303|PubMed:30131334};
DE EC=1.1.99.39 {ECO:0000269|PubMed:28827360, ECO:0000269|PubMed:30131334};
DE AltName: Full=D-malate dehydrogenase {ECO:0000305|PubMed:30131334};
DE EC=1.1.99.- {ECO:0000269|PubMed:28827360, ECO:0000269|PubMed:30131334};
GN Name=d2hgdh {ECO:0000303|PubMed:28827360, ECO:0000303|PubMed:30131334};
GN OrderedLocusNames=PST_0399 {ECO:0000312|EMBL:ABP78105.1};
OS Pseudomonas stutzeri (strain A1501).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=379731;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=A1501;
RX PubMed=18495935; DOI=10.1073/pnas.0801093105;
RA Yan Y., Yang J., Dou Y., Chen M., Ping S., Peng J., Lu W., Zhang W.,
RA Yao Z., Li H., Liu W., He S., Geng L., Zhang X., Yang F., Yu H., Zhan Y.,
RA Li D., Lin Z., Wang Y., Elmerich C., Lin M., Jin Q.;
RT "Nitrogen fixation island and rhizosphere competence traits in the genome
RT of root-associated Pseudomonas stutzeri A1501.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7564-7569(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, COFACTOR, DISRUPTION PHENOTYPE, AND SUBUNIT.
RC STRAIN=A1501;
RX PubMed=28827360; DOI=10.1073/pnas.1619034114;
RA Zhang W., Zhang M., Gao C., Zhang Y., Ge Y., Guo S., Guo X., Zhou Z.,
RA Liu Q., Zhang Y., Ma C., Tao F., Xu P.;
RT "Coupling between D-3-phosphoglycerate dehydrogenase and S-2-
RT hydroxyglutarate dehydrogenase drives bacterial L-serine synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E7574-E7582(2017).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, COFACTOR, DISRUPTION PHENOTYPE, INDUCTION, AND ACTIVITY
RP REGULATION.
RC STRAIN=A1501;
RX PubMed=30131334; DOI=10.1074/jbc.ra118.003897;
RA Guo X., Zhang M., Cao M., Zhang W., Kang Z., Xu P., Ma C., Gao C.;
RT "D-2-Hydroxyglutarate dehydrogenase plays a dual role in L-serine
RT biosynthesis and D-malate utilization in the bacterium Pseudomonas
RT stutzeri.";
RL J. Biol. Chem. 293:15513-15523(2018).
CC -!- FUNCTION: Catalyzes the dehydrogenation of (R)-2-hydroxyglutarate (D-2-
CC hydroxyglutarate or D-2-HG) to 2-oxoglutarate and of (R)-malate (D-
CC malate) to oxaloacetate. Is functionally tied to L-serine biosynthesis,
CC via its coupling with the D-3-phosphoglycerate dehydrogenase SerA,
CC encoded by the adjacent gene in the locus. Is required for the
CC utilization of D-2-hydroxyglutarate as well as D-malate as the sole
CC carbon source for growth of P.stutzeri. Active in vitro with artificial
CC electron acceptors such as 2,6-dichlorophenolindophenol (DCPIP) and
CC appears to couple with electron transfer flavoprotein (ETF) for
CC efficient oxidation of both D-2-hydroxyglutarate and D-malate in vivo.
CC Cannot catalyze the oxidation of L-2-hydroxyglutarate, D-lactate, D-
CC tartrate, D-2-hydroxybutanoate, D-mandelate, D-glycerate and D-
CC phenyllactate. {ECO:0000269|PubMed:28827360,
CC ECO:0000269|PubMed:30131334}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxyglutarate + A = 2-oxoglutarate + AH2;
CC Xref=Rhea:RHEA:38295, ChEBI:CHEBI:13193, ChEBI:CHEBI:15801,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:17499; EC=1.1.99.39;
CC Evidence={ECO:0000269|PubMed:28827360, ECO:0000269|PubMed:30131334};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38296;
CC Evidence={ECO:0000269|PubMed:28827360, ECO:0000269|PubMed:30131334};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-malate + A = AH2 + oxaloacetate; Xref=Rhea:RHEA:67460,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15588, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:17499; Evidence={ECO:0000269|PubMed:28827360,
CC ECO:0000269|PubMed:30131334};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67461;
CC Evidence={ECO:0000269|PubMed:30131334};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:28827360, ECO:0000269|PubMed:30131334};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:28827360};
CC -!- ACTIVITY REGULATION: Activated by Zn(2+) ions at low concentrations (10
CC uM) and inhibited by Zn(2+), Fe(2+) and Ni(2+) at high concentrations
CC (10 mM). {ECO:0000269|PubMed:30131334}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.17 mM for D-2-hydroxyglutarate (at pH 7.4 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:28827360};
CC KM=7.71 uM for electron transfer flavoprotein (at pH 7.4 and 37
CC degrees Celsius) {ECO:0000269|PubMed:28827360};
CC KM=210 uM for cytochrome c (at pH 7.4 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:28827360};
CC KM=3.61 mM for D-malate (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:30131334};
CC Vmax=4.56 umol/min/mg enzyme with D-2-hydroxyglutarate as substrate
CC and DCIP as the electron acceptor (at pH 7.4 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:28827360};
CC Vmax=7.50 umol/min/mg enzyme with D-2-hydroxyglutarate as substrate
CC and electron transfer flavoprotein (ETF) as the electron acceptor (at
CC pH 7.4 and 37 degrees Celsius) {ECO:0000269|PubMed:28827360};
CC Vmax=0.84 umol/min/mg enzyme with D-2-hydroxyglutarate as substrate
CC and cytochrome c as the electron acceptor (at pH 7.4 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:28827360};
CC Vmax=6.87 umol/min/mg enzyme with D-2-malate as substrate and DCIP as
CC the electron acceptor (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:30131334};
CC Note=kcat is 7.9 sec(-1) with D-2-hydroxyglutarate as substrate and
CC DCIP as the electron acceptor (at pH 7.4 and 37 degrees Celsius).
CC kcat is 13.0 sec(-1) with D-2-hydroxyglutarate as substrate and
CC electron transfer flavoprotein (ETF) as the electron acceptor (at pH
CC 7.4 and 37 degrees Celsius). kcat is 1.45 sec(-1) with D-2-
CC hydroxyglutarate as substrate and cytochrome c as the electron
CC acceptor (at pH 7.4 and 37 degrees Celsius) (PubMed:28827360). kcat
CC is 11.7 sec(-1) with D-malate as substrate and DCIP as the electron
CC acceptor (at pH 7.4 and 30 degrees Celsius) (PubMed:30131334).
CC {ECO:0000269|PubMed:28827360, ECO:0000269|PubMed:30131334};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:28827360}.
CC -!- INDUCTION: Expression is up-regulated by exogenously added D-2-
CC hydroxyglutarate or D-malate. {ECO:0000269|PubMed:30131334}.
CC -!- DISRUPTION PHENOTYPE: The deletion mutant is barely able to use D-2-HG
CC for growth and displays a relatively slower growth in a medium
CC containing glucose. Cells lacking this gene also show high accumulation
CC of extracellular and intracellular D-2-HG (PubMed:28827360). Moreover,
CC the mutant strain loses the ability to utilize D-malate for growth
CC (PubMed:30131334). {ECO:0000269|PubMed:28827360,
CC ECO:0000269|PubMed:30131334}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
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DR EMBL; CP000304; ABP78105.1; -; Genomic_DNA.
DR RefSeq; WP_011911635.1; NC_009434.1.
DR STRING; 379731.PST_0399; -.
DR EnsemblBacteria; ABP78105; ABP78105; PST_0399.
DR KEGG; psa:PST_0399; -.
DR eggNOG; COG0277; Bacteria.
DR HOGENOM; CLU_017779_4_1_6; -.
DR OMA; WSTIGGN; -.
DR Proteomes; UP000000233; Chromosome.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.45.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR016164; FAD-linked_Oxase-like_C.
DR InterPro; IPR004113; FAD-linked_oxidase_C.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR InterPro; IPR016171; Vanillyl_alc_oxidase_C-sub2.
DR Pfam; PF02913; FAD-oxidase_C; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF55103; SSF55103; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Metal-binding; Oxidoreductase; Reference proteome; Zinc.
FT CHAIN 1..464
FT /note="D-2-hydroxyglutarate dehydrogenase"
FT /id="PRO_0000454853"
FT DOMAIN 37..216
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 325
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 325
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 329
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 329
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 339
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 339
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 383
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 420
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 421
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 421
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
SQ SEQUENCE 464 AA; 51086 MW; B29FE342ED8E245E CRC64;
MTDPALIDEL KTLVEPGKVL TDADSLNAYG KDWTKHFAPA PSAIVFPKSI EQVQAIVRWA
NAHKVALVPS GGRTGLSAAA VAANGEVVVS FDYMNQILEF NEMDRTAVCQ PGVVTAQLQQ
FAEDKGLYYP VDFASAGSSQ IGGNIGTNAG GIKVIRYGMT RNWVAGMKVV TGKGDLLELN
KDLIKNATGY DLRQLFIGAE GTLGFVVEAT MRLERQPTNL TALVLGTPDF DSIMPVLHAF
QDKLDLTAFE FFSDKALAKV LGRGDVPAPF ETDCPFYALL EFEATTEERA EQALATFEHC
VEQGWVLDGV MSQSEQQLQN LWKLREYISE TISHWTPYKN DISVTVGKVP AFLKEIDAIV
GEHYPDFEIV WFGHIGDGNL HLNILKPDAM DKDEFFGKCA TVNKWVFETV QKYNGSISAE
HGVGMTKRDY LEYSRSPAEI EYMKAVKAVF DPNGIMNPGK IFAA
