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Database: UniProt/SWISS-PROT
Entry: DDL_MYCTU
LinkDB: DDL_MYCTU
Original site: DDL_MYCTU 
ID   DDL_MYCTU               Reviewed;         373 AA.
AC   P9WP31; L0TBF6; P95114;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   28-FEB-2018, entry version 27.
DE   RecName: Full=D-alanine--D-alanine ligase {ECO:0000255|HAMAP-Rule:MF_00047};
DE            EC=6.3.2.4 {ECO:0000255|HAMAP-Rule:MF_00047, ECO:0000269|PubMed:20956591, ECO:0000269|PubMed:23286234};
DE   AltName: Full=D-Ala-D-Ala ligase {ECO:0000255|HAMAP-Rule:MF_00047};
DE   AltName: Full=D-alanine:D-alanine ligase {ECO:0000303|PubMed:20956591, ECO:0000303|PubMed:23286234};
DE   AltName: Full=D-alanylalanine synthetase {ECO:0000255|HAMAP-Rule:MF_00047};
GN   Name=ddl {ECO:0000255|HAMAP-Rule:MF_00047,
GN   ECO:0000303|PubMed:20956591, ECO:0000303|PubMed:23286234};
GN   Synonyms=ddlA; OrderedLocusNames=Rv2981c; ORFNames=MTCY349.06;
OS   Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=9634230; DOI=10.1038/31159;
RA   Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M.,
RA   Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III,
RA   Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T.,
RA   Connor R., Davies R.M., Devlin K., Feltwell T., Gentles S., Hamlin N.,
RA   Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S.,
RA   Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A.,
RA   Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R.,
RA   Sulston J.E., Taylor K., Whitehead S., Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the
RT   complete genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=21969609; DOI=10.1074/mcp.M111.011627;
RA   Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B.,
RA   Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H.,
RA   Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S.,
RA   Katoch K., Katoch V.M., Kumar P., Chaerkady R., Ramachandran S.,
RA   Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high
RT   resolution mass spectrometry.";
RL   Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME
RP   REGULATION, KINETIC MECHANISM, AND PATHWAY.
RX   PubMed=23286234; DOI=10.1111/febs.12108;
RA   Prosser G.A., de Carvalho L.P.;
RT   "Kinetic mechanism and inhibition of Mycobacterium tuberculosis D-
RT   alanine:D-alanine ligase by the antibiotic D-cycloserine.";
RL   FEBS J. 280:1150-1166(2013).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP   ENZYME REGULATION, SUBUNIT, AND PATHWAY.
RC   STRAIN=H37Rv;
RX   PubMed=20956591; DOI=10.1128/AAC.00558-10;
RA   Bruning J.B., Murillo A.C., Chacon O., Barletta R.G.,
RA   Sacchettini J.C.;
RT   "Structure of the Mycobacterium tuberculosis D-alanine:D-alanine
RT   ligase, a target of the antituberculosis drug D-cycloserine.";
RL   Antimicrob. Agents Chemother. 55:291-301(2011).
CC   -!- FUNCTION: Catalyzes the ATP-driven ligation of two D-alanine
CC       molecules to form the D-alanyl-D-alanine dipeptide. This molecule
CC       is a key building block in peptidoglycan biosynthesis.
CC       {ECO:0000255|HAMAP-Rule:MF_00047, ECO:0000269|PubMed:20956591,
CC       ECO:0000269|PubMed:23286234}.
CC   -!- CATALYTIC ACTIVITY: ATP + 2 D-alanine = ADP + phosphate + D-
CC       alanyl-D-alanine. {ECO:0000255|HAMAP-Rule:MF_00047,
CC       ECO:0000269|PubMed:20956591, ECO:0000269|PubMed:23286234}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC       Note=Binds 2 magnesium or manganese ions per subunit.
CC       {ECO:0000250};
CC   -!- ENZYME REGULATION: Is inhibited by the antituberculous drug D-
CC       cycloserine (DCS), which is a structural analog of D-alanine
CC       (PubMed:20956591, PubMed:23286234). Is activated by K(+)
CC       (PubMed:23286234). {ECO:0000269|PubMed:20956591,
CC       ECO:0000269|PubMed:23286234}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.075 mM for D-Ala (first D-Ala binding site) (at pH 7.3)
CC         {ECO:0000269|PubMed:23286234};
CC         KM=3.6 mM for D-Ala (second D-Ala binding site) (at pH 7.3)
CC         {ECO:0000269|PubMed:23286234};
CC         KM=0.31 mM for ATP (at pH 7.3) {ECO:0000269|PubMed:23286234};
CC         Note=kcat is 9.7 sec(-1) (at pH 7.3).
CC         {ECO:0000269|PubMed:23286234};
CC   -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC       {ECO:0000255|HAMAP-Rule:MF_00047, ECO:0000305|PubMed:20956591,
CC       ECO:0000305|PubMed:23286234}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:20956591}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00047}.
CC   -!- MISCELLANEOUS: Follows an ordered ter-ter mechanism. ATP is the
CC       first substrate to bind and is necessary for subsequent binding of
CC       D-alanine or DCS. ADP is the final product to dissociate.
CC       {ECO:0000269|PubMed:23286234}.
CC   -!- SIMILARITY: Belongs to the D-alanine--D-alanine ligase family.
CC       {ECO:0000255|HAMAP-Rule:MF_00047}.
DR   EMBL; AL123456; CCP45786.1; -; Genomic_DNA.
DR   PIR; B70673; B70673.
DR   RefSeq; NP_217497.1; NC_000962.3.
DR   RefSeq; WP_003912011.1; NZ_KK339370.1.
DR   PDB; 3LWB; X-ray; 2.10 A; A/B=1-373.
DR   PDBsum; 3LWB; -.
DR   ProteinModelPortal; P9WP31; -.
DR   SMR; P9WP31; -.
DR   STRING; 83332.Rv2981c; -.
DR   ChEMBL; CHEMBL2030; -.
DR   PaxDb; P9WP31; -.
DR   EnsemblBacteria; CCP45786; CCP45786; Rv2981c.
DR   GeneID; 888415; -.
DR   KEGG; mtu:Rv2981c; -.
DR   TubercuList; Rv2981c; -.
DR   eggNOG; ENOG4105CPF; Bacteria.
DR   eggNOG; COG1181; LUCA.
DR   KO; K01921; -.
DR   OMA; YETKYTE; -.
DR   PhylomeDB; P9WP31; -.
DR   BioCyc; MetaCyc:G185E-7236-MONOMER; -.
DR   UniPathway; UPA00219; -.
DR   PRO; PR:P9WP31; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0008716; F:D-alanine-D-alanine ligase activity; IDA:MTBBASE.
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:0040007; P:growth; IMP:MTBBASE.
DR   GO; GO:0009252; P:peptidoglycan biosynthetic process; IDA:MTBBASE.
DR   GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.1490.20; -; 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   Pfam; PF07478; Dala_Dala_lig_C; 1.
DR   Pfam; PF01820; Dala_Dala_lig_N; 1.
DR   PIRSF; PIRSF039102; Ddl/VanB; 1.
DR   SUPFAM; SSF52440; SSF52440; 1.
DR   TIGRFAMs; TIGR01205; D_ala_D_alaTIGR; 1.
DR   PROSITE; PS50975; ATP_GRASP; 1.
DR   PROSITE; PS00843; DALA_DALA_LIGASE_1; 1.
DR   PROSITE; PS00844; DALA_DALA_LIGASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell shape;
KW   Cell wall biogenesis/degradation; Complete proteome; Cytoplasm;
KW   Ligase; Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW   Peptidoglycan synthesis; Reference proteome.
FT   CHAIN         1    373       D-alanine--D-alanine ligase.
FT                                /FTId=PRO_0000177844.
FT   DOMAIN      156    363       ATP-grasp. {ECO:0000255|HAMAP-
FT                                Rule:MF_00047}.
FT   NP_BIND     184    239       ATP. {ECO:0000255|HAMAP-Rule:MF_00047}.
FT   METAL       318    318       Magnesium or manganese 1.
FT                                {ECO:0000255|HAMAP-Rule:MF_00047}.
FT   METAL       330    330       Magnesium or manganese 1.
FT                                {ECO:0000255|HAMAP-Rule:MF_00047}.
FT   METAL       330    330       Magnesium or manganese 2.
FT                                {ECO:0000255|HAMAP-Rule:MF_00047}.
FT   METAL       332    332       Magnesium or manganese 2.
FT                                {ECO:0000255|HAMAP-Rule:MF_00047}.
FT   STRAND       11     18       {ECO:0000244|PDB:3LWB}.
FT   HELIX        26     37       {ECO:0000244|PDB:3LWB}.
FT   TURN         40     42       {ECO:0000244|PDB:3LWB}.
FT   STRAND       43     50       {ECO:0000244|PDB:3LWB}.
FT   STRAND       56     59       {ECO:0000244|PDB:3LWB}.
FT   HELIX       103    108       {ECO:0000244|PDB:3LWB}.
FT   STRAND      111    115       {ECO:0000244|PDB:3LWB}.
FT   HELIX       126    134       {ECO:0000244|PDB:3LWB}.
FT   STRAND      138    141       {ECO:0000244|PDB:3LWB}.
FT   HELIX       143    150       {ECO:0000244|PDB:3LWB}.
FT   HELIX       152    161       {ECO:0000244|PDB:3LWB}.
FT   STRAND      169    172       {ECO:0000244|PDB:3LWB}.
FT   HELIX       181    187       {ECO:0000244|PDB:3LWB}.
FT   STRAND      191    197       {ECO:0000244|PDB:3LWB}.
FT   TURN        200    203       {ECO:0000244|PDB:3LWB}.
FT   STRAND      205    207       {ECO:0000244|PDB:3LWB}.
FT   HELIX       210    212       {ECO:0000244|PDB:3LWB}.
FT   HELIX       213    221       {ECO:0000244|PDB:3LWB}.
FT   STRAND      225    231       {ECO:0000244|PDB:3LWB}.
FT   STRAND      234    244       {ECO:0000244|PDB:3LWB}.
FT   STRAND      250    252       {ECO:0000244|PDB:3LWB}.
FT   STRAND      256    259       {ECO:0000244|PDB:3LWB}.
FT   STRAND      266    271       {ECO:0000244|PDB:3LWB}.
FT   HELIX       273    277       {ECO:0000244|PDB:3LWB}.
FT   STRAND      283    287       {ECO:0000244|PDB:3LWB}.
FT   HELIX       292    308       {ECO:0000244|PDB:3LWB}.
FT   STRAND      313    322       {ECO:0000244|PDB:3LWB}.
FT   STRAND      325    334       {ECO:0000244|PDB:3LWB}.
FT   HELIX       342    349       {ECO:0000244|PDB:3LWB}.
FT   HELIX       354    367       {ECO:0000244|PDB:3LWB}.
SQ   SEQUENCE   373 AA;  39710 MW;  FD7838E8B7526B53 CRC64;
     MSANDRRDRR VRVAVVFGGR SNEHAISCVS AGSILRNLDS RRFDVIAVGI TPAGSWVLTD
     ANPDALTITN RELPQVKSGS GTELALPADP RRGGQLVSLP PGAGEVLESV DVVFPVLHGP
     YGEDGTIQGL LELAGVPYVG AGVLASAVGM DKEFTKKLLA ADGLPVGAYA VLRPPRSTLH
     RQECERLGLP VFVKPARGGS SIGVSRVSSW DQLPAAVARA RRHDPKVIVE AAISGRELEC
     GVLEMPDGTL EASTLGEIRV AGVRGREDSF YDFATKYLDD AAELDVPAKV DDQVAEAIRQ
     LAIRAFAAID CRGLARVDFF LTDDGPVINE INTMPGFTTI SMYPRMWAAS GVDYPTLLAT
     MIETTLARGV GLH
//
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