VANH_ENTFC
ID VANH_ENTFC Reviewed; 322 AA.
AC Q05709;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=D-specific alpha-keto acid dehydrogenase;
DE EC=1.1.1.-;
DE AltName: Full=Vancomycin resistance protein VanH;
GN Name=vanH;
OS Enterococcus faecium (Streptococcus faecium).
OG Plasmid pIP816.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=1352;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BM4147;
RX PubMed=1908809; DOI=10.1016/0378-1119(91)90405-z;
RA Arthur M., Molinas C., Dutka-Malen S., Courvalin P.;
RT "Structural relationship between the vancomycin resistance protein VanH and
RT 2-hydroxycarboxylic acid dehydrogenases.";
RL Gene 103:133-134(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BM4147; TRANSPOSON=Tn1546;
RX PubMed=8380148; DOI=10.1128/jb.175.1.117-127.1993;
RA Arthur M., Molinas C., Depardieu F., Courvalin P.;
RT "Characterization of Tn1546, a Tn3-related transposon conferring
RT glycopeptide resistance by synthesis of depsipeptide peptidoglycan
RT precursors in Enterococcus faecium BM4147.";
RL J. Bacteriol. 175:117-127(1993).
RN [3]
RP PROTEIN SEQUENCE OF 1-32, AND CHARACTERIZATION.
RC STRAIN=BM4147;
RX PubMed=1931965; DOI=10.1021/bi00107a007;
RA Bugg T.D.H., Wright G.D., Dutka-Malen S., Arthur M., Courvalin P.,
RA Walsh C.T.;
RT "Molecular basis for vancomycin resistance in Enterococcus faecium BM4147:
RT biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin
RT resistance proteins VanH and VanA.";
RL Biochemistry 30:10408-10415(1991).
RN [4]
RP FUNCTION.
RX PubMed=1522072; DOI=10.1128/jb.174.18.5982-5984.1992;
RA Handwerger S., Pucci M.J., Volk K.J., Liu J., Lee M.S.;
RT "The cytoplasmic peptidoglycan precursor of vancomycin-resistant
RT Enterococcus faecalis terminates in lactate.";
RL J. Bacteriol. 174:5982-5984(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19.
RX PubMed=1556077; DOI=10.1128/jb.174.8.2582-2591.1992;
RA Arthur M., Molinas C., Courvalin P.;
RT "The VanS-VanR two-component regulatory system controls synthesis of
RT depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147.";
RL J. Bacteriol. 174:2582-2591(1992).
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 {ECO:0000269|PubMed:1522072}.
CC -!- INDUCTION: By vancomycin, mediated by VanS/VanR.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; M64304; AAA24789.1; -; Genomic_DNA.
DR EMBL; M97297; AAA65955.1; -; Genomic_DNA.
DR PIR; JQ1191; JQ1191.
DR RefSeq; WP_001059542.1; NZ_WSZC01000116.1.
DR RefSeq; YP_001019036.1; NC_008821.1.
DR RefSeq; YP_001974797.1; NC_010980.1.
DR RefSeq; YP_002128398.1; NC_011140.1.
DR RefSeq; YP_004172616.1; NC_014959.1.
DR RefSeq; YP_006937549.1; NC_013317.1.
DR RefSeq; YP_007908269.1; NC_021170.1.
DR RefSeq; YP_976078.1; NC_008768.1.
DR AlphaFoldDB; Q05709; -.
DR SMR; Q05709; -.
DR SABIO-RK; Q05709; -.
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 1: Evidence at protein level;
KW Antibiotic resistance; Cell wall biogenesis/degradation;
KW Direct protein sequencing; NAD; Oxidoreductase; Plasmid.
FT CHAIN 1..322
FT /note="D-specific alpha-keto acid dehydrogenase"
FT /id="PRO_0000076023"
FT ACT_SITE 231
FT /evidence="ECO:0000250"
FT ACT_SITE 260
FT /evidence="ECO:0000250"
FT ACT_SITE 292
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 156..157
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 229..231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 292..295
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 322 AA; 35795 MW; 07CC31611C459D12 CRC64;
MNNIGITVYG CEQDEADAFH ALSPRFGVMA TIINANVSES NAKSAPFNQC ISVGHKSEIS
ASILLALKRA GVKYISTRSI GCNHIDTTAA KRMGITVDNV AYSPDSVADY TMMLILMAVR
NVKSIVRSVE KHDFRLDSDR GKVLSDMTVG VVGTGQIGKA VIERLRGFGC KVLAYSRSRS
IEVNYVPFDE LLQNSDIVTL HVPLNTDTHY IISHEQIQRM KQGAFLINTG RGPLVDTYEL
VKALENGKLG GAALDVLEGE EEFFYSDCTQ KPIDNQFLLK LQRMPNVIIT PHTAYYTEQA
LRDTVEKTIK NCLDFERRQE HE
