ID Q47755_ENTFC Unreviewed; 358 AA.
AC Q47755;
DT 01-NOV-1996, integrated into UniProtKB/TrEMBL.
DT 01-JUN-2001, sequence version 2.
DT 27-MAR-2024, entry version 171.
DE RecName: Full=D-alanine--D-alanine ligase {ECO:0000256|HAMAP-Rule:MF_00047};
DE EC=6.3.2.4 {ECO:0000256|HAMAP-Rule:MF_00047};
DE AltName: Full=D-Ala-D-Ala ligase {ECO:0000256|HAMAP-Rule:MF_00047};
DE AltName: Full=D-alanylalanine synthetase {ECO:0000256|HAMAP-Rule:MF_00047};
GN Name=ddl {ECO:0000256|HAMAP-Rule:MF_00047,
GN ECO:0000313|EMBL:AAQ12892.1};
GN Synonyms=ddlA {ECO:0000313|EMBL:BDP55704.1};
GN ORFNames=A5810_001545 {ECO:0000313|EMBL:OTN93669.1}, AWT83_02645
GN {ECO:0000313|EMBL:KWX17459.1}, B4W81_03435
GN {ECO:0000313|EMBL:AQY31119.1}, CUN04_02515
GN {ECO:0000313|EMBL:PQC77679.1}, DTX73_11850
GN {ECO:0000313|EMBL:KAA0689360.1}, EB12_01545
GN {ECO:0000313|EMBL:RBS31360.1}, EfmJHP36_01830
GN {ECO:0000313|EMBL:BDP55704.1}, GBM44_01060
GN {ECO:0000313|EMBL:KAB7616625.1}, GBM73_08820
GN {ECO:0000313|EMBL:KAB7577415.1}, GUI75_00340
GN {ECO:0000313|EMBL:NAB56418.1}, KYX88_10730
GN {ECO:0000313|EMBL:MBX4223285.1};
OS Enterococcus faecium (Streptococcus faecium).
OC Bacteria; Bacillota; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=1352 {ECO:0000313|EMBL:AAB17902.2};
RN [1] {ECO:0000313|EMBL:AAB17902.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=BM4147 {ECO:0000313|EMBL:AAB17902.2};
RX PubMed=8662022; DOI=10.1007/BF02338803;
RA Evers S., Casadewall B., Charles M., Dutka-Malen S., Galimand M.,
RA Courvalin P.;
RT "Evolution of structure and substrate specificity in D-alanine:D-alanine
RT ligases and related enzymes.";
RL J. Mol. Evol. 42:706-712(1996).
RN [2] {ECO:0000313|EMBL:AAB17902.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=BM4147 {ECO:0000313|EMBL:AAB17902.2};
RA van Bambeke F., Gholizadeh Y., Casadewall B., Courvalin P.;
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000313|EMBL:AAB17902.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=BM4147 {ECO:0000313|EMBL:AAB17902.2};
RX PubMed=11274474; DOI=10.1110/ps.39101;
RA Gholizadeh Y., Prevost M., Van Bambeke F., Casadewall B., Tulkens P.M.,
RA Courvalin P.;
RT "Sequencing of the ddl gene and modeling of the mutated D-alanine:D-alanine
RT ligase in glycopeptide-dependent strains of Enterococcus faecium.";
RL Protein Sci. 10:836-844(2001).
RN [4] {ECO:0000313|EMBL:AAQ12892.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=BM4524 {ECO:0000313|EMBL:AAQ12892.1};
RX PubMed=14617162; DOI=10.1046/j.1365-2958.2003.03771.x;
RA Depardieu F., Courvalin P., Msadek T.;
RT "A six amino acid deletion, partially overlapping the VanSB G2 ATP-binding
RT motif, leads to constitutive glycopeptide resistance in VanB-type
RT Enterococcus faecium.";
RL Mol. Microbiol. 50:1069-1083(2003).
RN [5] {ECO:0000313|EMBL:AHH83929.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=SAU16 {ECO:0000313|EMBL:AHH83929.1};
RA Santona A., Al-Qahtani A.A., Paglietti B., Bohol M.F.F., Senok A.,
RA Deligios M., Rubino S., Al-Ahdal M.N.;
RT "Emerging of a new VanB teicoplanin-resistant Enterococcus faecium strain
RT in Saudi Arabia.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000313|EMBL:RBS31360.1, ECO:0000313|Proteomes:UP000253144}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=131EA1 {ECO:0000313|EMBL:RBS31360.1,
RC ECO:0000313|Proteomes:UP000253144};
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Van Tyne D., Lebreton F., Saavedra J.T., Gilmore M.S.,
RA Manson Mcguire A., Clock S., Crupain M., Rangan U., Young S.,
RA Abouelleil A., Cao P., Chapman S.B., Griggs A., Priest M., Shea T.,
RA Wortman J., Nusbaum C., Birren B.;
RT "The Genome Sequence of Enterococcus faecium 131EA1.";
RL Submitted (JUN-2015) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000313|EMBL:KWX17459.1, ECO:0000313|Proteomes:UP000070452}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=D344RRF x C68 {ECO:0000313|EMBL:KWX17459.1,
RC ECO:0000313|Proteomes:UP000070452};
RA Garcia-Solache M.A., Lebreton F., Mclaughlin R.E., Whiteaker J.D.,
RA Gilmore M.S., Rice L.B.;
RT "Molecular Mechanisms for transfer of large genomic segments between
RT Enterococcus faecium strains.";
RL Submitted (JAN-2016) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000313|EMBL:AQY31119.1, ECO:0000313|Proteomes:UP000190755}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2014-VREF-268 {ECO:0000313|EMBL:AQY31119.1};
RA Kim H.M.;
RT "Non-typeable vancomycin-resistant E. faecium.";
RL Submitted (MAR-2017) to the EMBL/GenBank/DDBJ databases.
RN [9] {ECO:0000313|EMBL:OTN93669.1, ECO:0000313|Proteomes:UP000194885}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=7H8_DIV0219 {ECO:0000313|EMBL:OTN93669.1,
RC ECO:0000313|Proteomes:UP000194885};
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genomic Center for Infectious Diseases;
RA Earl A., Manson A., Schwartman J., Gilmore M., Abouelleil A., Cao P.,
RA Chapman S., Cusick C., Shea T., Young S., Neafsey D., Nusbaum C.,
RA Birren B.;
RT "The Genome Sequence of Enterococcus faecium 7H8_DIV0219.";
RL Submitted (MAY-2017) to the EMBL/GenBank/DDBJ databases.
RN [10] {ECO:0000313|EMBL:PQC77679.1, ECO:0000313|Proteomes:UP000239169}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CVM N59891F {ECO:0000313|EMBL:PQC77679.1,
RC ECO:0000313|Proteomes:UP000239169};
RA Tyson G.;
RT "Whole-genome sequencing based characterization of antimicrobial resistance
RT in Enterococcus.";
RL Pathog. Dis. 0:0-0(2018).
RN [11] {ECO:0000313|EMBL:KAA0689360.1, ECO:0000313|Proteomes:UP000448762}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=R.A73 {ECO:0000313|EMBL:KAA0689360.1,
RC ECO:0000313|Proteomes:UP000448762};
RA El-Jeni R., Ghedira K., Abdelhak S., El-Bour M., Bouhaouala-Zahar B.;
RT "High quality draft genome sequencing of Enterococcus faecium exhibiting
RT probiotic potential isolated from mucus of freshwater fish.";
RL Submitted (JUL-2018) to the EMBL/GenBank/DDBJ databases.
RN [12] {ECO:0000313|EMBL:NAB56418.1, ECO:0000313|Proteomes:UP000482088}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=BIOML-A3 {ECO:0000313|EMBL:NAB56418.1,
RC ECO:0000313|Proteomes:UP000482088};
RX PubMed=31477907; DOI=.1038/s41591-019-0559-3;
RA Poyet M., Groussin M., Gibbons S.M., Avila-Pacheco J., Jiang X.,
RA Kearney S.M., Perrotta A.R., Berdy B., Zhao S., Lieberman T.D.,
RA Swanson P.K., Smith M., Roesemann S., Alexander J.E., Rich S.A., Livny J.,
RA Vlamakis H., Clish C., Bullock K., Deik A., Scott J., Pierce K.A.,
RA Xavier R.J., Alm E.J.;
RT "A library of human gut bacterial isolates paired with longitudinal
RT multiomics data enables mechanistic microbiome research.";
RL Nat. Med. 25:1442-1452(2019).
RN [13] {ECO:0000313|Proteomes:UP000446843, ECO:0000313|Proteomes:UP000469871}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VRECG10 {ECO:0000313|EMBL:KAB7616625.1,
RC ECO:0000313|Proteomes:UP000446843}, and VRECG27
RC {ECO:0000313|EMBL:KAB7577415.1, ECO:0000313|Proteomes:UP000469871};
RA Chilambi G.S., Nordstrom H.R., Evans D.R., Ferrolino J., Hayden R.T.,
RA Maron G.M., Vo A.N., Gilmore M.S., Wolf J., Rosch J.W., Van Tyne D.;
RT "Evolutionary dynamics of vancomycin-resistant Enterococcus faecium during
RT gastrointestinal tract colonization and bloodstream infection in
RT immunocompromised pediatric patients.";
RL Submitted (OCT-2019) to the EMBL/GenBank/DDBJ databases.
RN [14] {ECO:0000313|EMBL:MBX4223285.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=EF215 {ECO:0000313|EMBL:MBX4223285.1};
RX PubMed=35150575; DOI=10.1093/jas/skac030;
RA Shridhar P.B., Amachawadi R.G., Tokach M., Patel I., Gangiredla J.,
RA Mammel M., Nagaraja T.G.;
RT "Whole genome sequence analyses-based assessment of virulence potential and
RT antimicrobial susceptibilities and resistance of Enterococcus faecium
RT strains isolated from commercial swine and cattle probiotic products.";
RL J. Anim. Sci. 100:skac030-skac030(2022).
RN [15] {ECO:0000313|EMBL:BDP55704.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=JHP36 {ECO:0000313|EMBL:BDP55704.1};
RA Hashimoto Y., Suzuki M., Tomita H.;
RT "Analysis of enterococcal linear plasmids.";
RL Submitted (AUG-2022) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Cell wall formation. {ECO:0000256|HAMAP-Rule:MF_00047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + 2 D-alanine = ADP + D-alanyl-D-alanine + H(+) +
CC phosphate; Xref=Rhea:RHEA:11224, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57416,
CC ChEBI:CHEBI:57822, ChEBI:CHEBI:456216; EC=6.3.2.4;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00047};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000256|PIRSR:PIRSR039102-3};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|PIRSR:PIRSR039102-3};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000256|PIRSR:PIRSR039102-3};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|ARBA:ARBA00001936};
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC {ECO:0000256|HAMAP-Rule:MF_00047}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00047}.
CC -!- SIMILARITY: Belongs to the D-alanine--D-alanine ligase family.
CC {ECO:0000256|ARBA:ARBA00010871, ECO:0000256|HAMAP-Rule:MF_00047}.
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DR EMBL; U39790; AAB17902.2; -; Genomic_DNA.
DR EMBL; AF550665; AAQ12892.1; -; Genomic_DNA.
DR EMBL; KF823966; AHH83929.1; -; Genomic_DNA.
DR EMBL; CP019992; AQY31119.1; -; Genomic_DNA.
DR EMBL; AP026586; BDP55704.1; -; Genomic_DNA.
DR EMBL; QOVC01000009; KAA0689360.1; -; Genomic_DNA.
DR EMBL; WEFP01000001; KAB7577415.1; -; Genomic_DNA.
DR EMBL; WEGG01000001; KAB7616625.1; -; Genomic_DNA.
DR EMBL; LRHK01000001; KWX17459.1; -; Genomic_DNA.
DR EMBL; JAIFOC010000092; MBX4223285.1; -; Genomic_DNA.
DR EMBL; WXSK01000001; NAB56418.1; -; Genomic_DNA.
DR EMBL; NGKW01000003; OTN93669.1; -; Genomic_DNA.
DR EMBL; PTVN01000009; PQC77679.1; -; Genomic_DNA.
DR EMBL; LEQJ01000009; RBS31360.1; -; Genomic_DNA.
DR RefSeq; WP_002293424.1; NZ_WYDL01000009.1.
DR STRING; 1352.AL014_11300; -.
DR GeneID; 66496441; -.
DR PATRIC; fig|1352.655.peg.1326; -.
DR OMA; RVDFFYV; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000070452; Unassembled WGS sequence.
DR Proteomes; UP000190755; Chromosome.
DR Proteomes; UP000194885; Unassembled WGS sequence.
DR Proteomes; UP000239169; Unassembled WGS sequence.
DR Proteomes; UP000253144; Unassembled WGS sequence.
DR Proteomes; UP000446843; Unassembled WGS sequence.
DR Proteomes; UP000448762; Unassembled WGS sequence.
DR Proteomes; UP000469871; Unassembled WGS sequence.
DR Proteomes; UP000482088; Unassembled WGS sequence.
DR Proteomes; UP001061325; Chromosome.
DR Proteomes; UP001139644; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008716; F:D-alanine-D-alanine ligase activity; IEA:UniProtKB-UniRule.
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-UniRule.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.20; -; 1.
DR Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1.
DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR HAMAP; MF_00047; Dala_Dala_lig; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR000291; D-Ala_lig_Van_CS.
DR InterPro; IPR005905; D_ala_D_ala.
DR InterPro; IPR011095; Dala_Dala_lig_C.
DR InterPro; IPR011127; Dala_Dala_lig_N.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR NCBIfam; TIGR01205; D_ala_D_alaTIGR; 1.
DR PANTHER; PTHR23132; D-ALANINE--D-ALANINE LIGASE; 1.
DR PANTHER; PTHR23132:SF25; D-ALANINE--D-ALANINE LIGASE A; 1.
DR Pfam; PF07478; Dala_Dala_lig_C; 1.
DR Pfam; PF01820; Dala_Dala_lig_N; 1.
DR PIRSF; PIRSF039102; Ddl/VanB; 1.
DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR SUPFAM; SSF52440; PreATP-grasp domain; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS00843; DALA_DALA_LIGASE_1; 1.
DR PROSITE; PS00844; DALA_DALA_LIGASE_2; 1.
PE 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW ProRule:PRU00409};
KW Cell shape {ECO:0000256|ARBA:ARBA00022960, ECO:0000256|HAMAP-
KW Rule:MF_00047};
KW Cell wall biogenesis/degradation {ECO:0000256|ARBA:ARBA00023316,
KW ECO:0000256|HAMAP-Rule:MF_00047};
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00047};
KW Ligase {ECO:0000256|ARBA:ARBA00022598, ECO:0000256|HAMAP-Rule:MF_00047};
KW Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|PIRSR:PIRSR039102-3};
KW Manganese {ECO:0000256|ARBA:ARBA00023211, ECO:0000256|PIRSR:PIRSR039102-3};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR039102-3};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW ProRule:PRU00409};
KW Peptidoglycan synthesis {ECO:0000256|ARBA:ARBA00022984, ECO:0000256|HAMAP-
KW Rule:MF_00047}.
FT DOMAIN 136..341
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR039102-3"
FT BINDING 308
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR039102-3"
FT BINDING 308
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR039102-3"
FT BINDING 310
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR039102-3"
SQ SEQUENCE 358 AA; 40247 MW; 0801F31DB1FA9FEC CRC64;
MKITLLYGGR SAEHEVSILS AFSVLNAIYY NYYQVQLVFI TKEGQWVKGP LLTEKPASKD
VLHLSWDPSG QTEEGFTGKV INPGEIKEEG AIVFPVLHGP NGEDGTIQGF LETLNMPYVG
AGVLTSACAM DKIMTKYILQ AAGVPQVPYV PVLKNQWKEN PKKVFDQCEG SLLYPMFVKP
ANMGSSVGIT KAENREELQN ALATAYQYDS RAIVEQGIEA REIEVAVLGN EDVRTTLPGE
VVKDVAFYDY EAKYINNKIE MQIPAEVPEE VYQKAQEYAK LAYTMLGGSG LSRCDFFLTN
KNELFLNELN SMPGFTEFSM YPLLWENMGL KYGDLIEELI QLGMNRYHQR QSFFEKNE
//
