DAC_STRSR
ID DAC_STRSR Reviewed; 406 AA.
AC P15555; Q06656;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=D-alanyl-D-alanine carboxypeptidase;
DE Short=DD-carboxypeptidase;
DE Short=DD-peptidase;
DE EC=3.4.16.4;
DE Flags: Precursor;
OS Streptomyces sp. (strain R61).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=31952;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3830154; DOI=10.1111/j.1432-1033.1987.tb10669.x;
RA Duez C., Piron-Fraipont C., Joris B., Dusart J., Urdea M.S., Martial J.A.,
RA Frere J.-M., Ghuysen J.-M.;
RT "Primary structure of the Streptomyces R61 extracellular DD-peptidase. 1.
RT Cloning into Streptomyces lividans and nucleotide sequence of the gene.";
RL Eur. J. Biochem. 162:509-518(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION.
RX PubMed=7925404; DOI=10.1111/j.1432-1033.1994.01079.x;
RA Duez C., Piron-Fraipont C., Joris B., Dusart J., Urdea M.S., Martial J.A.,
RA Frere J.-M., Ghuysen J.-M.;
RT "Primary structure of the Streptomyces R61 extracellular DD-peptidase. 1.
RT Cloning into Streptomyces lividans and nucleotide sequence of the gene.";
RL Eur. J. Biochem. 224:1079-1079(1994).
RN [3]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=3030739; DOI=10.1111/j.1432-1033.1987.tb10670.x;
RA Joris B., Jacques P., Frere J.-M., Ghuysen J.-M., van Beeumen J.;
RT "Primary structure of the Streptomyces R61 extracellular DD-peptidase. 2.
RT Amino acid sequence data.";
RL Eur. J. Biochem. 162:519-524(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-91.
RX PubMed=2175384; DOI=10.1007/bf00315803;
RA Piron-Fraipont C., Lenzini M.V., Dusart J., Ghuysen J.-M.;
RT "Transcriptional analysis of the DD-peptidase/penicillin-binding protein-
RT encoding dac gene of Streptomyces R61: use of the promoter and signal
RT sequences in a secretion vector.";
RL Mol. Gen. Genet. 223:114-120(1990).
RN [5]
RP 3D-STRUCTURE MODELING.
RX PubMed=2386365; DOI=10.1128/aac.34.7.1342;
RA Knox J.R., Pratt R.F.;
RT "Different modes of vancomycin and D-alanyl-D-alanine peptidase binding to
RT cell wall peptide and a possible role for the vancomycin resistance
RT protein.";
RL Antimicrob. Agents Chemother. 34:1342-1347(1990).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=3997832; DOI=10.1016/s0021-9258(18)88993-1;
RA Kelly J.A., Knox J.R., Moews P.C., Hite G.J., Bartolone J.B., Zhao H.,
RA Joris B., Frere J.-M., Ghuysen J.-M.;
RT "2.8-A structure of penicillin-sensitive D-alanyl carboxypeptidase-
RT transpeptidase from Streptomyces R61 and complexes with beta-lactams.";
RL J. Biol. Chem. 260:6449-6458(1985).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=7490745; DOI=10.1006/jmbi.1995.0613;
RA Kelly J.A., Kuzin A.P.;
RT "The refined crystallographic structure of a DD-peptidase penicillin-target
RT enzyme at 1.6-A resolution.";
RL J. Mol. Biol. 254:223-236(1995).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 32-380 IN COMPLEX WITH
RP SUBSTRATES, AND ACTIVE SITE.
RX PubMed=12215418; DOI=10.1016/s0022-2836(02)00742-8;
RA McDonough M.A., Anderson J.W., Silvaggi N.R., Pratt R.F., Knox J.R.,
RA Kelly J.A.;
RT "Structures of two kinetic intermediates reveal species specificity of
RT penicillin-binding proteins.";
RL J. Mol. Biol. 322:111-122(2002).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.12 ANGSTROMS) OF 32-380 IN COMPLEX WITH
RP SUBSTRATES, AND ACTIVE SITE.
RX PubMed=12564922; DOI=10.1021/bi0268955;
RA Silvaggi N.R., Anderson J.W., Brinsmade S.R., Pratt R.F., Kelly J.A.;
RT "The crystal structure of phosphonate-inhibited D-Ala-D-Ala peptidase
RT reveals an analogue of a tetrahedral transition state.";
RL Biochemistry 42:1199-1208(2003).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.07 ANGSTROMS) OF 32-380 IN COMPLEX WITH SUBSTRATE
RP ANALOG, AND ACTIVE SITE.
RX PubMed=15581896; DOI=10.1016/j.jmb.2004.10.076;
RA Silvaggi N.R., Josephine H.R., Kuzin A.P., Nagarajan R., Pratt R.F.,
RA Kelly J.A.;
RT "Crystal structures of complexes between the R61 DD-peptidase and
RT peptidoglycan-mimetic beta-lactams: a non-covalent complex with a 'perfect
RT penicillin'.";
RL J. Mol. Biol. 345:521-533(2005).
CC -!- FUNCTION: Catalyzes distinct carboxypeptidation and transpeptidation
CC reactions during the last stages of wall peptidoglycan synthesis.
CC Mistaking a beta-lactam antibiotic molecule for a normal substrate
CC (i.e. a D-alanyl-D-alanine-terminated peptide), it becomes immobilized
CC in the form of a long-lived, serine-ester-linked acyl enzyme and thus
CC behave as penicillin-binding protein (PBP).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: (Ac)2-L-Lys-D-Ala-|-D-Ala. Also
CC transpeptidation of peptidyl-alanyl moieties that are N-acyl
CC substituents of D-alanine.; EC=3.4.16.4;
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the peptidase S12 family. {ECO:0000305}.
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DR EMBL; X05109; CAA28756.1; -; Genomic_DNA.
DR EMBL; X55810; CAB97254.1; -; Genomic_DNA.
DR PIR; S48220; S48220.
DR PDB; 1CEF; X-ray; 2.04 A; A=32-380.
DR PDB; 1CEG; X-ray; 1.80 A; A=32-380.
DR PDB; 1HVB; X-ray; 1.17 A; A=32-380.
DR PDB; 1IKG; X-ray; 1.90 A; A=32-380.
DR PDB; 1IKI; X-ray; 1.25 A; A=32-380.
DR PDB; 1MPL; X-ray; 1.12 A; A=32-380.
DR PDB; 1PW1; X-ray; 1.20 A; A=32-380.
DR PDB; 1PW8; X-ray; 1.30 A; A=32-380.
DR PDB; 1PWC; X-ray; 1.10 A; A=32-380.
DR PDB; 1PWD; X-ray; 1.20 A; A=32-380.
DR PDB; 1PWG; X-ray; 1.07 A; A=32-380.
DR PDB; 1SCW; X-ray; 1.13 A; A=32-380.
DR PDB; 1SDE; X-ray; 1.15 A; A=32-378.
DR PDB; 1YQS; X-ray; 1.05 A; A=32-380.
DR PDB; 3PTE; X-ray; 1.60 A; A=32-380.
DR PDBsum; 1CEF; -.
DR PDBsum; 1CEG; -.
DR PDBsum; 1HVB; -.
DR PDBsum; 1IKG; -.
DR PDBsum; 1IKI; -.
DR PDBsum; 1MPL; -.
DR PDBsum; 1PW1; -.
DR PDBsum; 1PW8; -.
DR PDBsum; 1PWC; -.
DR PDBsum; 1PWD; -.
DR PDBsum; 1PWG; -.
DR PDBsum; 1SCW; -.
DR PDBsum; 1SDE; -.
DR PDBsum; 1YQS; -.
DR PDBsum; 3PTE; -.
DR AlphaFoldDB; P15555; -.
DR SMR; P15555; -.
DR ChEMBL; CHEMBL3350; -.
DR DrugBank; DB03820; (2S,5R,6R)-6-({(6S)-6-[(Ammonioacetyl)amino]-6-carboxylatohexanoyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate.
DR DrugBank; DB02514; (2Z)-3-{[Oxido(oxo)phosphoranyl]oxy}-2-phenylacrylate.
DR DrugBank; DB04488; (6S)-N-[(2S,3R,6R,7R)-3-(Acetyloxymethyl)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octan-7-yl]-6-[(2-aminoacetyl)amino]-7-hydroxy-7-oxoheptanimidate.
DR DrugBank; DB04340; 2-[(Dioxidophosphoranyl)oxy]benzoate.
DR DrugBank; DB00456; Cefalotin.
DR DrugBank; DB02136; Cephalosporin analog.
DR DrugBank; DB03313; Cephalosporin C.
DR DrugBank; DB03450; Cephalothin Group.
DR DrugBank; DB01786; D-Alanine.
DR DrugBank; DB03843; Formaldehyde.
DR DrugBank; DB01868; Glycyl-L-a-Aminopimelyl-E-(D-2-Aminoethyl)Phosphonate.
DR DrugBank; DB03927; Glycyl-L-alpha-amino-epsilon-pimelyl-D-alanine.
DR DrugBank; DB02578; N-[(6S)-6-Carboxy-6-(glycylamino)hexanoyl]-D-alanyl-D-alanine.
DR MEROPS; S12.001; -.
DR BRENDA; 3.4.16.4; 1284.
DR UniPathway; UPA00219; -.
DR EvolutionaryTrace; P15555; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0009002; F:serine-type D-Ala-D-Ala carboxypeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR001466; Beta-lactam-related.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR Pfam; PF00144; Beta-lactamase; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cell shape;
KW Cell wall biogenesis/degradation; Direct protein sequencing; Hydrolase;
KW Peptidoglycan synthesis; Protease; Secreted; Signal.
FT SIGNAL 1..31
FT CHAIN 32..380
FT /note="D-alanyl-D-alanine carboxypeptidase"
FT /id="PRO_0000017050"
FT PROPEP 381..406
FT /id="PRO_0000017051"
FT REGION 387..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 93
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000269|PubMed:12215418,
FT ECO:0000269|PubMed:12564922, ECO:0000269|PubMed:15581896"
FT BINDING 151..154
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12215418,
FT ECO:0000269|PubMed:12564922, ECO:0000269|PubMed:15581896"
FT BINDING 190..192
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12215418,
FT ECO:0000269|PubMed:12564922, ECO:0000269|PubMed:15581896"
FT BINDING 316
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12215418,
FT ECO:0000269|PubMed:12564922, ECO:0000269|PubMed:15581896"
FT BINDING 330..332
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12215418,
FT ECO:0000269|PubMed:12564922, ECO:0000269|PubMed:15581896"
FT BINDING 357..358
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12215418,
FT ECO:0000269|PubMed:12564922, ECO:0000269|PubMed:15581896"
FT HELIX 39..51
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 66..75
FT /evidence="ECO:0007829|PDB:1YQS"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 95..108
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:1PWG"
FT HELIX 133..137
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:1SCW"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 168..176
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 192..206
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 210..217
FT /evidence="ECO:0007829|PDB:1YQS"
FT TURN 218..223
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:1YQS"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 275..286
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 293..299
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 316..319
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 325..333
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:1YQS"
FT STRAND 346..358
FT /evidence="ECO:0007829|PDB:1YQS"
FT HELIX 360..374
FT /evidence="ECO:0007829|PDB:1YQS"
SQ SEQUENCE 406 AA; 42917 MW; C2C77B53A29099E9 CRC64;
MVSGTVGRGT ALGAVLLALL AVPAQAGTAA AADLPAPDDT GLQAVLHTAL SQGAPGAMVR
VDDNGTIHQL SEGVADRATG RAITTTDRFR VGSVTKSFSA VVLLQLVDEG KLDLDASVNT
YLPGLLPDDR ITVRQVMSHR SGLYDYTNDM FAQTVPGFES VRNKVFSYQD LITLSLKHGV
TNAPGAAYSY SNTNFVVAGM LIEKLTGHSV ATEYQNRIFT PLNLTDTFYV HPDTVIPGTH
ANGYLTPDEA GGALVDSTEQ TVSWAQSAGA VISSTQDLDT FFSALMSGQL MSAAQLAQMQ
QWTTVNSTQG YGLGLRRRDL SCGISVYGHT GTVQGYYTYA FASKDGKRSV TALANTSNNV
NVLNTMARTL ESAFCGKPTT AKLRSATSSA TTVERHEDIA PGIARD
