VANY_ENTFA
ID VANY_ENTFA Reviewed; 268 AA.
AC Q47746;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=D-alanyl-D-alanine carboxypeptidase {ECO:0000305};
DE Short=D,D-carboxypeptidase {ECO:0000303|PubMed:30016658, ECO:0000303|PubMed:8631706};
DE Short=D-Ala-D-Ala carboxypeptidase {ECO:0000305};
DE EC=3.4.17.- {ECO:0000305};
GN Name=vanYB {ECO:0000303|PubMed:8631706}; OrderedLocusNames=EF_2297;
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], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, INDUCTION, AND SUBCELLULAR LOCATION.
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).
RN [3] {ECO:0007744|PDB:5HNM}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 72-268 IN COMPLEX WITH ZINC.
RA Stogios P.J.;
RT "To be published.";
RL Submitted (JAN-2016) to the PDB data bank.
RN [4] {ECO:0007744|PDB:5ZHF, ECO:0007744|PDB:5ZHW, ECO:0007744|PDB:6A6A}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 52-268 IN COMPLEXES WITH ZINC;
RP D-ALA-D-ALA DIPEPTIDE AND D-ALA, COFACTOR, SUBUNIT, ACTIVE SITE, AND
RP REACTION MECHANISM.
RC STRAIN=ATCC 700802 / V583;
RX PubMed=30016658; DOI=10.1016/j.ijbiomac.2018.07.081;
RA Kim H.S., Hahn H., Kim J., Jang D.M., Lee J.Y., Back J.M., Im H.N., Kim H.,
RA Han B.W., Suh S.W.;
RT "Structural basis for the substrate recognition of peptidoglycan
RT pentapeptides by Enterococcus faecalis VanYB.";
RL Int. J. Biol. Macromol. 119:335-344(2018).
CC -!- FUNCTION: Carboxypeptidase that cleaves the C-terminal D-alanine
CC residue from the peptidoglycan-derived pentapeptide L-Ala-gamma-D-Glu-
CC L-Lys-D-Ala-D-Ala in vitro. Therefore, should contribute in vivo to the
CC hydrolysis of the D-alanyl-D-alanine-containing peptidoglycan
CC precursors. May increase the level of glycopeptide antibiotics
CC resistance by decreasing the availability of D-Ala-D-Ala termini from
CC the cell surface, which constitute the antibiotic target residues.
CC {ECO:0000269|PubMed:8631706}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:30016658};
CC -!- ACTIVITY REGULATION: Carboxypeptidase activity is insensitive to beta-
CC lactams since it is not affected by penicillin G or ampicillin and is
CC inhibited only by very high concentrations of cefalotin and cefoxitin.
CC {ECO:0000269|PubMed:8631706}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:30016658}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:8631706};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: By vancomycin, mediated by VanS/VanR. Part of the VanB-type
CC operon associated to vancomycin resistance in E.faecalis V583.
CC {ECO:0000269|PubMed:8631706}.
CC -!- SIMILARITY: Belongs to the peptidase M15B family. {ECO:0000305}.
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DR EMBL; U35369; AAB05624.1; -; Genomic_DNA.
DR EMBL; AE016830; AAO82024.1; -; Genomic_DNA.
DR RefSeq; NP_815954.1; NC_004668.1.
DR RefSeq; WP_002368695.1; NZ_KE136528.1.
DR PDB; 5HNM; X-ray; 2.30 A; A/B/C/D/E/F=72-268.
DR PDB; 5ZHF; X-ray; 1.65 A; A/B=52-268.
DR PDB; 5ZHW; X-ray; 2.18 A; A/B=52-268.
DR PDB; 6A6A; X-ray; 2.26 A; A/B=52-268.
DR PDBsum; 5HNM; -.
DR PDBsum; 5ZHF; -.
DR PDBsum; 5ZHW; -.
DR PDBsum; 6A6A; -.
DR AlphaFoldDB; Q47746; -.
DR SMR; Q47746; -.
DR STRING; 226185.EF_2297; -.
DR EnsemblBacteria; AAO82024; AAO82024; EF_2297.
DR KEGG; efa:EF2297; -.
DR PATRIC; fig|226185.45.peg.1235; -.
DR eggNOG; COG1876; Bacteria.
DR HOGENOM; CLU_054193_2_1_9; -.
DR OMA; SNEPWHY; -.
DR Proteomes; UP000001415; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1380.10; -; 1.
DR InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf.
DR InterPro; IPR003709; Pept_M15B.
DR Pfam; PF02557; VanY; 1.
DR SUPFAM; SSF55166; SSF55166; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Carboxypeptidase; Cell membrane;
KW Cell shape; Cell wall biogenesis/degradation; Hydrolase; Membrane;
KW Metal-binding; Peptidoglycan synthesis; Protease; Reference proteome;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..268
FT /note="D-alanyl-D-alanine carboxypeptidase"
FT /id="PRO_0000195471"
FT TRANSMEM 25..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 238
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:30016658"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30016658"
FT BINDING 179..181
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30016658"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:30016658"
FT BINDING 188
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:30016658,
FT ECO:0007744|PDB:5HNM"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:30016658,
FT ECO:0007744|PDB:5HNM"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:30016658,
FT ECO:0007744|PDB:5HNM"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:5HNM"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 122..134
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 148..164
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:5ZHF"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 205..215
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:5ZHF"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 247..256
FT /evidence="ECO:0007829|PDB:5ZHF"
FT HELIX 260..266
FT /evidence="ECO:0007829|PDB:5ZHF"
SQ SEQUENCE 268 AA; 30382 MW; 93B4E8D20C2B865A CRC64;
MEKSNYHSNV NHHKRHMKQS GEKRAFLWAF IISFTVCTLF LGWRLVSVLE ATQLPPIPAT
HTGSGTGVAE NPEENTLATA KEQGDEQEWS LILVNRQNPI PAQYDVELEQ LSNGERIDIR
ISPYLQDLFD AARADGVYPI VASGYRTTEK QQEIMDEKVA EYKAKGYTSA QAKAEAETWV
AVPGTSEHQL GLAVDINADG IHSTGNEVYR WLDENSYRFG FIRRYPPDKT EITGVSNEPW
HYRYVGIEAA TKIYHQGLCL EEYLNTEK
