D2HDH_XANCL
ID D2HDH_XANCL Reviewed; 472 AA.
AC P0DV35;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=D-2-hydroxyglutarate dehydrogenase {ECO:0000303|PubMed:34555022};
DE Short=D2HGDH;
DE EC=1.1.99.39 {ECO:0000269|PubMed:34555022};
GN ORFNames=XVT_549 {ECO:0000312|EMBL:CDN17902.1};
OS Xanthomonas citri pv. viticola (strain LMG 965 / NCPPB 2475 / ICMP 3867 /
OS CFBP 7660) (Xanthomonas campestris pv. viticola).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Xanthomonadales;
OC Xanthomonadaceae; Xanthomonas.
OX NCBI_TaxID=1232713;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LMG 965 / NCPPB 2475 / ICMP 3867 / CFBP 7660;
RX PubMed=25085494; DOI=10.1128/aem.01654-14;
RA Midha S., Patil P.B.;
RT "Genomic insights into the evolutionary origin of Xanthomonas axonopodis
RT pv. citri and its ecological relatives.";
RL Appl. Environ. Microbiol. 80:6266-6279(2014).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=34555022; DOI=10.1371/journal.pcbi.1009446;
RA Rembeza E., Engqvist M.K.M.;
RT "Experimental and computational investigation of enzyme functional
RT annotations uncovers misannotation in the EC 1.1.3.15 enzyme class.";
RL PLoS Comput. Biol. 17:e1009446-e1009446(2021).
CC -!- FUNCTION: Catalyzes the dehydrogenation of (R)-2-hydroxyglutarate (D-2-
CC hydroxyglutarate) to 2-oxoglutarate. Has also a low activity on D-
CC malate in vitro (PubMed:34555022). Is functionally tied to L-serine
CC biosynthesis, via its coupling with the D-3-phosphoglycerate
CC dehydrogenase SerA, encoded by the adjacent gene in the locus (By
CC similarity). Active in vitro with the artificial electron acceptor 2,6-
CC dichlorophenolindophenol (DCPIP), but not with NAD, NADP, or cytochrome
CC c. Also displays a very low oxidase activity in vitro on D-2-
CC hydroxyglutarate and L-2-hydroxyglutarate with O2 as the electron
CC acceptor, but this activity is most likely not physiological
CC (PubMed:34555022). {ECO:0000250|UniProtKB:A4VGK4,
CC ECO:0000269|PubMed:34555022}.
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:34555022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38296;
CC Evidence={ECO:0000305};
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:34555022};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A4VGK4};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:A4VGK4};
CC -!- ACTIVITY REGULATION: Activated by Zn(2+) ions.
CC {ECO:0000250|UniProtKB:A4VGK4}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.08 mM for D-2-hydroxyglutarate (at pH 7.4 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:34555022};
CC KM=5.03 mM for D-malate (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:34555022};
CC Note=kcat is 5.9 sec(-1) with D-2-hydroxyglutarate as substrate and
CC DCPIP as electron acceptor (at pH 7.4 and 25 degrees Celsius). kcat
CC is 0.04 sec(-1) with D-malate as substrate and DCPIP as electron
CC acceptor (at pH 7.4 and 25 degrees Celsius).
CC {ECO:0000269|PubMed:34555022};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:A4VGK4}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
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DR EMBL; CBZT010000001; CDN17902.1; -; Genomic_DNA.
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; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
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; Zinc.
FT CHAIN 1..472
FT /note="D-2-hydroxyglutarate dehydrogenase"
FT /id="PRO_0000454852"
FT DOMAIN 36..215
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 323
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 323
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 327
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 327
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 337
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 337
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 379
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 381
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 419
FT /ligand="(R)-2-hydroxyglutarate"
FT /ligand_id="ChEBI:CHEBI:15801"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
FT BINDING 419
FT /ligand="(R)-malate"
FT /ligand_id="ChEBI:CHEBI:15588"
FT /evidence="ECO:0000250|UniProtKB:Q8N465"
SQ SEQUENCE 472 AA; 51032 MW; 826F102F4DE2B4A3 CRC64;
MTDPRILSLQ QAVPALRLKT EPADLEHYGR DWTRRWTPNP LAIALPGSVE EVQAVVRWAN
AQAVAVVPSG GRTGLSGGAV AANGELVLSL ERLNKPLDFN AVDRTLTVQA GMPLEAVHNA
AREQGLVYPV DFAARGSCSI GGNIATNAGG IRVIRYGNTR EWVAGLKVVT GSGELLELNN
ALVKNSSGYD FRHLMIGSEG TLGIVVEATL RLTDPPPPSN VMLLALPSFD VLMQVFAAFR
AQLRLEAFEF FTDRALEHVL AHGAQAPFAE IHPYYVVTEF AAGDEAQEAA AMAAFETCME
QGWVSDGVIS QSDAQAAQLW RLREGITEAL ARYTPYKNDV SVRISAMPAF LAETQALLHD
AYPDFDVVWF GHIGDGNLHI NVLKPDATSQ ADFVAACDQV TKLLAQALQR FDGSISAEHG
IGLVKKSYLW STRSAEEIAL MRGIKHVLDP HLLLNPGKLF ETHDAPTNIP AG
