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   03-AUG-2022, entry version 128.
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; Firmicutes; 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   OMA; CELAFNC; -.
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   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   Pfam; PF00389; 2-Hacid_dh; 1.
DR   Pfam; PF02826; 2-Hacid_dh_C; 1.
DR   SUPFAM; SSF51735; SSF51735; 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