DDH_HALMT
ID DDH_HALMT Reviewed; 308 AA.
AC Q2VEQ7; I3R656;
DT 14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=D-2-hydroxyacid dehydrogenase;
DE Short=D2-HDH;
DE EC=1.1.1.-;
DE AltName: Full=D-specific 2-hydroxyacid dehydrogenase;
GN Name=ddh; Synonyms=serA5; OrderedLocusNames=HFX_2024;
OS Haloferax mediterranei (strain ATCC 33500 / DSM 1411 / JCM 8866 / NBRC
OS 14739 / NCIMB 2177 / R-4) (Halobacterium mediterranei).
OC Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Haloferacales;
OC Haloferacaceae; Haloferax.
OX NCBI_TaxID=523841;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, KINETIC
RP PARAMETERS, SUBSTRATE SPECIFICITY, AND SUBUNIT.
RC STRAIN=ATCC 33500 / DSM 1411 / JCM 8866 / NBRC 14739 / NCIMB 2177 / R-4;
RX PubMed=17049749; DOI=10.1016/j.bbagen.2006.08.024;
RA Domenech J., Ferrer J.;
RT "A new D-2-hydroxyacid dehydrogenase with dual coenzyme-specificity from
RT Haloferax mediterranei, sequence analysis and heterologous
RT overexpression.";
RL Biochim. Biophys. Acta 1760:1667-1674(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33500 / DSM 1411 / JCM 8866 / NBRC 14739 / NCIMB 2177 / R-4;
RX PubMed=22843593; DOI=10.1128/jb.00880-12;
RA Han J., Zhang F., Hou J., Liu X., Li M., Liu H., Cai L., Zhang B., Chen Y.,
RA Zhou J., Hu S., Xiang H.;
RT "Complete genome sequence of the metabolically versatile halophilic
RT archaeon Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-
RT hydroxyvalerate) producer.";
RL J. Bacteriol. 194:4463-4464(2012).
CC -!- FUNCTION: Catalyzes the stereospecific NAD(P)H-dependent reduction of
CC 2-ketocarboxylic acids into the corresponding D-2-hydroxycarboxylic
CC acids. Can use both NADPH or NADH as reductant, displaying a marked
CC preference for NADPH over NADH. Shows a broad substrate specificity,
CC although it displays a marked preference for the 2-ketocarboxylic acids
CC having an unbranched chain of 4-5 carbon atoms.
CC {ECO:0000269|PubMed:17049749}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.31 mM for 2-ketoisoleucine (in the presence of NADPH, at pH 8.5
CC and 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=11.9 mM for 2-ketoisoleucine (in the presence of NADH, at pH 8.5
CC and 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=3.77 mM for 2-ketoisocaproate (in the presence of NADPH, at pH 8.5
CC and 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=13.9 mM for 2-ketoisocaproate (in the presence of NADH, at pH 8.5
CC and 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=13.45 mM for 2-ketobutyrate (in the presence of NADPH, at pH 8.5
CC and 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=106 mM for 2-ketobutyrate (in the presence of NADH, at pH 8.5 and
CC 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=21.96 mM for pyruvate (in the presence of NADPH, at pH 5 and 40
CC degrees Celsius) {ECO:0000269|PubMed:17049749};
CC KM=0.046 mM for NADPH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC KM=0.33 mM for NADH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=1.733 umol/min/mg enzyme for the reduction of 2-ketoisoleucine
CC by NADPH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=1.02 umol/min/mg enzyme for the reduction of 2-ketoisoleucine by
CC NADH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=1.47 umol/min/mg enzyme for the reduction of 2-ketoisocaproate
CC by NADPH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=0.94 umol/min/mg enzyme for the reduction of 2-ketoisocaproate
CC by NADH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=2.09 umol/min/mg enzyme for the reduction of 2-ketobutyrate by
CC NADPH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=2.1 umol/min/mg enzyme for the reduction of 2-ketobutyrate by
CC NADH (at pH 8.5 and 40 degrees Celsius)
CC {ECO:0000269|PubMed:17049749};
CC Vmax=0.8 umol/min/mg enzyme for the reduction of pyruvate by NADPH
CC (at pH 5 and 40 degrees Celsius) {ECO:0000269|PubMed:17049749};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:17049749}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; DQ223970; ABB30004.1; -; Genomic_DNA.
DR EMBL; CP001868; AFK19716.1; -; Genomic_DNA.
DR RefSeq; WP_004059362.1; NZ_CP039139.1.
DR PDB; 5MH5; X-ray; 1.40 A; A/B=1-308.
DR PDB; 5MH6; X-ray; 1.35 A; A/B/C/D=1-308.
DR PDB; 5MHA; X-ray; 1.57 A; A/B=1-308.
DR PDBsum; 5MH5; -.
DR PDBsum; 5MH6; -.
DR PDBsum; 5MHA; -.
DR AlphaFoldDB; Q2VEQ7; -.
DR SMR; Q2VEQ7; -.
DR STRING; 523841.HFX_2024; -.
DR EnsemblBacteria; AFK19716; AFK19716; HFX_2024.
DR GeneID; 40155066; -.
DR KEGG; hme:HFX_2024; -.
DR eggNOG; arCOG01757; Archaea.
DR HOGENOM; CLU_019796_1_0_2; -.
DR OMA; HVAGWSP; -.
DR OrthoDB; 36410at2157; -.
DR BioCyc; MetaCyc:MON-17694; -.
DR BRENDA; 1.1.1.272; 2566.
DR SABIO-RK; Q2VEQ7; -.
DR Proteomes; UP000006469; Chromosome.
DR GO; GO:0031406; F:carboxylic acid binding; IDA:UniProtKB.
DR GO; GO:0070404; F:NADH binding; IDA:UniProtKB.
DR GO; GO:0070402; F:NADPH binding; IDA:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR GO; GO:0019752; P:carboxylic acid metabolic process; IDA:UniProtKB.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; NAD; NADP; Oxidoreductase.
FT CHAIN 1..308
FT /note="D-2-hydroxyacid dehydrogenase"
FT /id="PRO_0000414497"
FT ACT_SITE 226
FT /evidence="ECO:0000250"
FT ACT_SITE 255
FT /evidence="ECO:0000250"
FT ACT_SITE 274
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 145..146
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9T0"
FT BINDING 224..226
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9T0"
FT BINDING 250
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9T0"
FT BINDING 274..277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9T0"
FT STRAND 5..9
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 10..14
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 18..24
FT /evidence="ECO:0007829|PDB:5MH6"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 54..58
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 74..80
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 92..108
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 110..118
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 145..156
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:5MH6"
FT TURN 201..205
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:5MH6"
FT HELIX 282..299
FT /evidence="ECO:0007829|PDB:5MH6"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:5MHA"
SQ SEQUENCE 308 AA; 33336 MW; 20D4FB8CE01D64AA CRC64;
MHIERLAVDE SVGRAMPPQR FIEALSDLGV PVEFAGEDEQ FGPGDAVASF GHRDAFLDAD
WVHCIRAGYD EFPVGVYEEA GTYLTNSTGI HGTTVGETVA GYMLTFARRL HAYRDAQHDH
AWDLPRYEEP FTLAGERVCV VGLGTLGRGV VDRAAALGME VVGVRRSGDP VDNVSTVYTP
DRLHEAIADA RFVVLATPLT DETEGMVAAP EFETMREDAS LVNVARGPVV VESDLVAALD
SGDIAGAALD VFSEEPLPED SPLWDFEDVL ITPHVSAATS KYHEDVAALI RENIEKIATG
DELTNRVV
