ID VANH_ENTFA Reviewed; 323 AA.
AC Q47748;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-APR-2003, sequence version 2.
DT 27-MAR-2024, entry version 132.
DE RecName: Full=D-specific alpha-keto acid dehydrogenase;
DE EC=1.1.1.-;
DE AltName: Full=Vancomycin B-type resistance protein VanHB;
GN Name=vanHB; OrderedLocusNames=EF_2295;
OS Enterococcus faecalis (strain ATCC 700802 / V583).
OC Bacteria; Bacillota; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=226185;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 700802 / V583;
RX PubMed=8631706; DOI=10.1128/jb.178.5.1302-1309.1996;
RA Evers S., Courvalin P.;
RT "Regulation of VanB-type vancomycin resistance gene expression by the
RT VanS(B)-VanR(B) two-component regulatory system in Enterococcus faecalis
RT V583.";
RL J. Bacteriol. 178:1302-1309(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700802 / V583;
RX PubMed=12663927; DOI=10.1126/science.1080613;
RA Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R.,
RA Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,
RA Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C.,
RA DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C.,
RA Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M.,
RA Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.;
RT "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus
RT faecalis.";
RL Science 299:2071-2074(2003).
CC -!- FUNCTION: Required for high-level resistance to glycopeptides
CC antibiotics. Catalyzes the reduction of 2-keto acids to 2-D-hydroxy
CC acids that give rise to peptidoglycan precursors that terminate in the
CC depsipeptide D-alanine-2-lactate rather than the dipeptide D-alanine-D-
CC alanine thus preventing vancomycin binding.
CC -!- INDUCTION: By vancomycin, mediated by VanS/VanR. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; U35369; AAB05626.1; -; Genomic_DNA.
DR EMBL; AE016830; AAO82022.1; -; Genomic_DNA.
DR RefSeq; NP_815952.1; NC_004668.1.
DR RefSeq; WP_002368693.1; NZ_KE136528.1.
DR AlphaFoldDB; Q47748; -.
DR SMR; Q47748; -.
DR STRING; 226185.EF_2295; -.
DR EnsemblBacteria; AAO82022; AAO82022; EF_2295.
DR KEGG; efa:EF2295; -.
DR PATRIC; fig|226185.45.peg.1237; -.
DR eggNOG; COG1052; Bacteria.
DR HOGENOM; CLU_019796_1_1_9; -.
DR Proteomes; UP000001415; Chromosome.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd12185; HGDH_LDH_like; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR43026; 2-HYDROXYACID DEHYDROGENASE HOMOLOG 1-RELATED; 1.
DR PANTHER; PTHR43026:SF1; 2-HYDROXYACID DEHYDROGENASE HOMOLOG 1-RELATED; 1.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF52283; Formate/glycerate dehydrogenase catalytic domain-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00670; D_2_HYDROXYACID_DH_2; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 3: Inferred from homology;
KW Antibiotic resistance; Cell wall biogenesis/degradation; NAD;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..323
FT /note="D-specific alpha-keto acid dehydrogenase"
FT /id="PRO_0000076022"
FT ACT_SITE 232
FT /evidence="ECO:0000250"
FT ACT_SITE 261
FT /evidence="ECO:0000250"
FT ACT_SITE 293
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 157..158
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 230..232
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 293..296
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT CONFLICT 216..217
FT /note="RQ -> SE (in Ref. 1; AAB05626)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 35266 MW; 87294FD0B77132DA CRC64;
MRKSMGITVF GCEQDEANAF RTLSPDFHII PTLISDAISA DNAKLAAGNQ CISVGHKSEV
SEATILALRK VGVKYISTRS IGCNHIDTTA AERMGISVGT VAYSPDSVAD YALMLMLMAI
RGAKSTIHAV AQQNFRLDCV RGKELRDMTV GVIGTGHIGQ AVVKRLRGFG CRVLAYDNSR
KIEADYVQLD ELLKNSDIVT LHVPLCADTR HLIGQRQIGE MKQGAFLINT GRGALVDTGS
LVEALGSGKL GGAALDVLEG EDQFVYTDCS QKVLDHPFLS QLLRMPNVII TPHTAYYTER
VLRDTTEKTI RNCLNFERSL QHE
//
