ID DAC_ACTSP Reviewed; 538 AA. AC P39045; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 13-SEP-2023, entry version 118. DE RecName: Full=D-alanyl-D-alanine carboxypeptidase; DE Short=DD-carboxypeptidase; DE Short=DD-peptidase; DE EC=3.4.16.4; DE AltName: Full=Penicillin-binding protein; DE Short=PBP; DE Flags: Precursor; GN Name=dac; OS Actinomadura sp. (strain R39). OC Bacteria; Actinomycetota; Actinomycetes; Streptosporangiales; OC Thermomonosporaceae; Actinomadura. OX NCBI_TaxID=72570; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 50-87. RX PubMed=1554361; DOI=10.1042/bj2820781; RA Granier B., Duez C., Lepage S., Englebert S., Dusart J., Dideberg O., RA van Beeumen J., Frere J.-M., Ghuysen J.-M.; RT "Primary and predicted secondary structures of the Actinomadura R39 RT extracellular DD-peptidase, a penicillin-binding protein (PBP) related to RT the Escherichia coli PBP4."; RL Biochem. J. 282:781-788(1992). RN [2] RP ERRATUM OF PUBMED:1554361. RX PubMed=1417760; RA Granier B., Duez C., Lepage S., Englebert S., Dusart J., Dideberg O., RA van Beeumen J., Frere J.-M., Ghuysen J.-M.; RL Biochem. J. 286:981-982(1992). RN [3] RP PROTEIN SEQUENCE OF 95-101, AND SUBSTRATE-BINDING SITE. RX PubMed=7305936; DOI=10.1042/bj1930083; RA Duez C., Joris B., Frere J.-M., Ghuysen J.-M., van Beeumen J.; RT "The penicillin-binding site in the exocellular DD-carboxypeptidase- RT transpeptidase of Actinomadura R39."; RL Biochem. J. 193:83-86(1981). RN [4] RP ACTIVITY REGULATION. RX PubMed=11160090; DOI=10.1128/jb.183.5.1595-1599.2001; RA Duez C., Vanhove M., Gallet X., Bouillenne F., Docquier J.-D., Brans A., RA Frere J.-M.; RT "Purification and characterization of PBP4a, a new low-molecular-weight RT penicillin-binding protein from Bacillus subtilis."; RL J. Bacteriol. 183:1595-1599(2001). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 50-515 OF APOENZYME AND COMPLEX RP WITH NITROCEFIN, AND PROCESSING OF C-TERMINUS. RX PubMed=15987687; DOI=10.1074/jbc.m503271200; RA Sauvage E., Herman R., Petrella S., Duez C., Bouillenne F., Frere J.-M., RA Charlier P.; RT "Crystal structure of the Actinomadura R39 DD-peptidase reveals new domains RT in penicillin-binding proteins."; RL J. Biol. Chem. 280:31249-31256(2005). CC -!- FUNCTION: Removes C-terminal D-alanyl residues from sugar-peptide cell CC wall precursors. 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 -!- ACTIVITY REGULATION: Inhibited by benzylpenicillin, cephaloridine, CC ampicillin and cetiofur. {ECO:0000269|PubMed:11160090}. CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- SIMILARITY: Belongs to the peptidase S13 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X64790; CAA46023.1; -; Genomic_DNA. DR PIR; S22409; S22409. DR PDB; 1W79; X-ray; 1.80 A; A/B/C/D=50-538. DR PDB; 1W8Q; X-ray; 2.85 A; A/B/C/D=50-538. DR PDB; 1W8Y; X-ray; 2.40 A; A/B/C/D=50-538. DR PDB; 2VGJ; X-ray; 2.40 A; A/B/C/D=50-538. DR PDB; 2VGK; X-ray; 2.25 A; A/B/C/D=50-538. DR PDB; 2WKE; X-ray; 2.20 A; A/B/C/D=50-515. DR PDB; 2XDM; X-ray; 2.40 A; A/B/C/D=50-515. DR PDB; 2XK1; X-ray; 2.80 A; A/B/C/D=50-515. DR PDB; 2XLN; X-ray; 2.40 A; A/B/C/D=50-538. DR PDB; 2Y4A; X-ray; 2.70 A; A/B/C/D=50-515. DR PDB; 2Y55; X-ray; 2.60 A; A/B/C/D=50-515. DR PDB; 2Y59; X-ray; 2.50 A; A/B/C/D=50-515. DR PDB; 3ZCZ; X-ray; 2.60 A; A/B/C/D=50-516. DR PDB; 3ZVT; X-ray; 3.10 A; A/B/C/D=50-515. DR PDB; 3ZVW; X-ray; 2.00 A; A/B/C/D=50-515. DR PDB; 4B4X; X-ray; 2.65 A; A/B/C/D=50-515. DR PDB; 4B4Z; X-ray; 2.20 A; A/B/C/D=50-515. DR PDB; 4BEN; X-ray; 2.15 A; A/B/C/D=50-515. DR PDBsum; 1W79; -. DR PDBsum; 1W8Q; -. DR PDBsum; 1W8Y; -. DR PDBsum; 2VGJ; -. DR PDBsum; 2VGK; -. DR PDBsum; 2WKE; -. DR PDBsum; 2XDM; -. DR PDBsum; 2XK1; -. DR PDBsum; 2XLN; -. DR PDBsum; 2Y4A; -. DR PDBsum; 2Y55; -. DR PDBsum; 2Y59; -. DR PDBsum; 3ZCZ; -. DR PDBsum; 3ZVT; -. DR PDBsum; 3ZVW; -. DR PDBsum; 4B4X; -. DR PDBsum; 4B4Z; -. DR PDBsum; 4BEN; -. DR AlphaFoldDB; P39045; -. DR SMR; P39045; -. DR BindingDB; P39045; -. DR ChEMBL; CHEMBL6016; -. DR DrugBank; DB04742; (2R)-2-{(1R)-2-oxo-1-[(2-thienylacetyl)amino]ethyl}-5,6-dihydro-2h-1,3-thiazine-4-carboxylic acid. DR MEROPS; S13.002; -. DR BRENDA; 3.4.16.4; 129. DR SABIO-RK; P39045; -. DR UniPathway; UPA00219; -. DR EvolutionaryTrace; P39045; -. 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 GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW. DR Gene3D; 3.50.80.20; D-Ala-D-Ala carboxypeptidase C, peptidase S13; 1. DR Gene3D; 3.40.710.10; DD-peptidase/beta-lactamase superfamily; 2. DR InterPro; IPR012338; Beta-lactam/transpept-like. DR InterPro; IPR000667; Peptidase_S13. DR NCBIfam; TIGR00666; PBP4; 1. DR PANTHER; PTHR30023; D-ALANYL-D-ALANINE CARBOXYPEPTIDASE; 1. DR PANTHER; PTHR30023:SF0; PENICILLIN-SENSITIVE CARBOXYPEPTIDASE A; 1. DR Pfam; PF02113; Peptidase_S13; 1. DR PRINTS; PR00922; DADACBPTASE3. DR SUPFAM; SSF56601; beta-lactamase/transpeptidase-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic resistance; Carboxypeptidase; Cell shape; KW Cell wall biogenesis/degradation; Direct protein sequencing; Hydrolase; KW Peptidoglycan synthesis; Protease; Secreted; Signal. FT SIGNAL 1..49 FT /evidence="ECO:0000269|PubMed:1554361" FT CHAIN 50..515 FT /note="D-alanyl-D-alanine carboxypeptidase" FT /id="PRO_0000027240" FT PROPEP 516..538 FT /note="Removed in mature form" FT /id="PRO_0000308945" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 146..319 FT /note="Absent in class-A beta-lactamases" FT ACT_SITE 98 FT /note="Acyl-ester intermediate" FT ACT_SITE 101 FT /note="Proton acceptor" FT ACT_SITE 347 FT /evidence="ECO:0000250" FT BINDING 459 FT /ligand="substrate" FT CONFLICT 100..101 FT /note="MK -> GV (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 51..61 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 71..78 FT /evidence="ECO:0007829|PDB:1W79" FT TURN 79..81 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 84..89 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 97..99 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 100..111 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 117..126 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 137..141 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:2Y4A" FT HELIX 149..161 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:2VGJ" FT STRAND 171..174 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 195..197 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:2Y4A" FT TURN 208..211 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 212..221 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 234..236 FT /evidence="ECO:0007829|PDB:1W79" FT TURN 237..239 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 240..244 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 247..249 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 258..260 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 267..275 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 290..304 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 313..315 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 326..335 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 336..346 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 349..364 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 369..382 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 395..397 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 403..405 FT /evidence="ECO:0007829|PDB:2XDM" FT HELIX 406..417 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 418..421 FT /evidence="ECO:0007829|PDB:2XK1" FT HELIX 422..428 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 437..440 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 441..443 FT /evidence="ECO:0007829|PDB:1W79" FT TURN 451..455 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 457..459 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 466..473 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 480..487 FT /evidence="ECO:0007829|PDB:1W79" FT STRAND 490..492 FT /evidence="ECO:0007829|PDB:1W79" FT HELIX 495..508 FT /evidence="ECO:0007829|PDB:1W79" SQ SEQUENCE 538 AA; 54974 MW; 58A8300C32802E7B CRC64; MKQSSPEPLR PRRTGGRGGA RRAAALVTIP LLPMTLLGAS PALADASGAR LTELREDIDA ILEDPALEGA VSGVVVVDTA TGEELYSRDG GEQLLPASNM KLFTAAAALE VLGADHSFGT EVAAESAPGR RGEVQDLYLV GRGDPTLSAE DLDAMAAEVA ASGVRTVRGD LYADDTWFDS ERLVDDWWPE DEPYAYSAQI SALTVAHGER FDTGVTEVSV TPAAEGEPAD VDLGAAEGYA ELDNRAVTGA AGSANTLVID RPVGTNTIAV TGSLPADAAP VTALRTVDEP AALAGHLFEE ALESNGVTVK GDVGLGGVPA DWQDAEVLAD HTSAELSEIL VPFMKFSNNG HAEMLVKSIG QETAGAGTWD AGLVGVEEAL SGLGVDTAGL VLNDGSGLSR GNLVTADTVV DLLGQAGSAP WAQTWSASLP VAGESDPFVG GTLANRMRGT AAEGVVEAKT GTMSGVSALS GYVPGPEGEL AFSIVNNGHS GPAPLAVQDA IAVRLAEYAG HQAPEGARMM RGPVQGSGEL ECSWVQAC //