DACA_ECOLI
ID DACA_ECOLI Reviewed; 403 AA.
AC P0AEB2; P04287; P77106;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=D-alanyl-D-alanine carboxypeptidase DacA;
DE Short=DD-carboxypeptidase;
DE Short=DD-peptidase;
DE EC=3.4.16.4;
DE AltName: Full=Beta-lactamase;
DE EC=3.5.2.6;
DE AltName: Full=Penicillin-binding protein 5;
DE Short=PBP-5;
DE Flags: Precursor;
GN Name=dacA; Synonyms=pfv; OrderedLocusNames=b0632, JW0627;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Broome-Smith J.K.;
RL Submitted (APR-1984) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3279397; DOI=10.1093/nar/16.4.1617;
RA Broome-Smith J.K., Ioannidis I., Edelman A., Spratt B.G.;
RT "Nucleotide sequences of the penicillin-binding protein 5 and 6 genes of
RT Escherichia coli.";
RL Nucleic Acids Res. 16:1617-1617(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 108-336, AND MUTANT DACA11191.
RX PubMed=6319180; DOI=10.1016/0014-5793(84)80166-0;
RA Broome-Smith J.K., Spratt B.G.;
RT "An amino acid substitution that blocks the deacylation step in the enzyme
RT mechanism of penicillin-binding protein 5 of Escherichia coli.";
RL FEBS Lett. 165:185-189(1984).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39.
RC STRAIN=K12;
RX PubMed=3316191; DOI=10.1128/jb.169.12.5692-5699.1987;
RA Takase I., Ishino F., Wachi M., Kamata H., Doi M., Asoh S., Matsuzawa H.,
RA Ohta T., Matsuhashi M.;
RT "Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia
RT coli chromosome.";
RL J. Bacteriol. 169:5692-5699(1987).
RN [9]
RP PROTEIN SEQUENCE OF 30-57.
RX PubMed=7042389; DOI=10.1016/0014-5793(82)80840-5;
RA Waxman D.J., Amanuma H., Strominger J.L.;
RT "Amino acid sequence homologies between Escherichia coli penicillin-binding
RT protein 5 and class A beta-lactamases.";
RL FEBS Lett. 139:159-163(1982).
RN [10]
RP MUTAGENESIS OF LYS-213.
RX PubMed=1597468; DOI=10.1016/s0021-9258(19)49922-5;
RA Malhotra K.T., Nicholas R.A.;
RT "Substitution of lysine 213 with arginine in penicillin-binding protein 5
RT of Escherichia coli abolishes D-alanine carboxypeptidase activity without
RT affecting penicillin binding.";
RL J. Biol. Chem. 267:11386-11391(1992).
RN [11]
RP DOMAINS.
RX PubMed=8424800;
RA van der Linden M.P.G., de Haan L., Keck W.;
RT "Domain organization of penicillin-binding protein 5 from Escherichia coli
RT analysed by C-terminal truncation.";
RL Biochem. J. 289:593-598(1993).
RN [12]
RP IDENTIFICATION BY 2D-GEL.
RX PubMed=9298644; DOI=10.1002/elps.1150180805;
RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.;
RT "Escherichia coli proteome analysis using the gene-protein database.";
RL Electrophoresis 18:1243-1251(1997).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 30-386 OF MUTANT ASP-134.
RX PubMed=10967102; DOI=10.1074/jbc.m004471200;
RA Davies C., White S.W., Nicholas R.A.;
RT "Crystal structure of a deacylation-defective mutant of penicillin-binding
RT protein 5 at 2.3-A resolution.";
RL J. Biol. Chem. 276:616-623(2001).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 30-386 OF WILD-TYPE AND MUTANT
RP ASP-134, AND MUTAGENESIS OF 101-GLY--LYS-121.
RX PubMed=14555648; DOI=10.1074/jbc.m310177200;
RA Nicholas R.A., Krings S., Tomberg J., Nicola G., Davies C.;
RT "Crystal structure of wild-type penicillin-binding protein 5 from
RT Escherichia coli. Implications for deacylation of the acyl-enzyme
RT complex.";
RL J. Biol. Chem. 278:52826-52833(2003).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 30-386 IN COMPLEX WITH SUBSTRATE
RP ANALOG, AND REACTION MECHANISM.
RX PubMed=15938610; DOI=10.1021/bi0473004;
RA Nicola G., Peddi S., Stefanova M., Nicholas R.A., Gutheil W.G., Davies C.;
RT "Crystal structure of Escherichia coli penicillin-binding protein 5 bound
RT to a tripeptide boronic acid inhibitor: a role for Ser-110 in
RT deacylation.";
RL Biochemistry 44:8207-8217(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 -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-lactam + H2O = a substituted beta-amino acid;
CC Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627,
CC ChEBI:CHEBI:140347; EC=3.5.2.6;
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein;
CC Cytoplasmic side. Note=N-terminal lies in the periplasmic space.
CC -!- SIMILARITY: Belongs to the peptidase S11 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB40832.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; X06479; CAA29774.1; -; Genomic_DNA.
DR EMBL; M18276; AAA24553.1; -; Genomic_DNA.
DR EMBL; U82598; AAB40832.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC73733.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA35275.1; -; Genomic_DNA.
DR EMBL; L07636; AAA66340.1; -; Genomic_DNA.
DR PIR; A28536; ZPECP5.
DR RefSeq; NP_415165.1; NC_000913.3.
DR RefSeq; WP_001092082.1; NZ_STEB01000031.1.
DR PDB; 1HD8; X-ray; 2.30 A; A=30-386.
DR PDB; 1NJ4; X-ray; 1.90 A; A=30-392.
DR PDB; 1NZO; X-ray; 1.85 A; A=30-392.
DR PDB; 1NZU; X-ray; 2.00 A; A=30-392.
DR PDB; 1SDN; X-ray; 2.50 A; A=30-392.
DR PDB; 1Z6F; X-ray; 1.60 A; A=30-392.
DR PDB; 3BEB; X-ray; 2.00 A; A=30-386.
DR PDB; 3BEC; X-ray; 1.60 A; A=30-386.
DR PDB; 3MZD; X-ray; 1.90 A; A=30-386.
DR PDB; 3MZE; X-ray; 2.10 A; A=30-386.
DR PDB; 3MZF; X-ray; 1.50 A; A=30-386.
DR PDB; 5J8X; X-ray; 2.53 A; A=30-392.
DR PDB; 6NTZ; X-ray; 2.20 A; A=1-403.
DR PDBsum; 1HD8; -.
DR PDBsum; 1NJ4; -.
DR PDBsum; 1NZO; -.
DR PDBsum; 1NZU; -.
DR PDBsum; 1SDN; -.
DR PDBsum; 1Z6F; -.
DR PDBsum; 3BEB; -.
DR PDBsum; 3BEC; -.
DR PDBsum; 3MZD; -.
DR PDBsum; 3MZE; -.
DR PDBsum; 3MZF; -.
DR PDBsum; 5J8X; -.
DR PDBsum; 6NTZ; -.
DR AlphaFoldDB; P0AEB2; -.
DR SMR; P0AEB2; -.
DR BioGRID; 4260698; 270.
DR DIP; DIP-47947N; -.
DR IntAct; P0AEB2; 9.
DR STRING; 511145.b0632; -.
DR ChEMBL; CHEMBL2354204; -.
DR DrugBank; DB01602; Bacampicillin.
DR DrugBank; DB04647; BOC-GAMMA-D-GLU-L-LYS(CBZ)-D-BOROALA.
DR DrugBank; DB00578; Carbenicillin.
DR DrugBank; DB09319; Carindacillin.
DR DrugBank; DB00274; Cefmetazole.
DR DrugBank; DB01329; Cefoperazone.
DR DrugBank; DB01331; Cefoxitin.
DR DrugBank; DB09050; Ceftolozane.
DR DrugBank; DB01147; Cloxacillin.
DR DrugBank; DB01000; Cyclacillin.
DR DrugCentral; P0AEB2; -.
DR MEROPS; S11.008; -.
DR jPOST; P0AEB2; -.
DR PaxDb; P0AEB2; -.
DR PRIDE; P0AEB2; -.
DR EnsemblBacteria; AAC73733; AAC73733; b0632.
DR EnsemblBacteria; BAA35275; BAA35275; BAA35275.
DR GeneID; 66671094; -.
DR GeneID; 945222; -.
DR KEGG; ecj:JW0627; -.
DR KEGG; eco:b0632; -.
DR PATRIC; fig|511145.12.peg.662; -.
DR EchoBASE; EB0197; -.
DR eggNOG; COG1686; Bacteria.
DR HOGENOM; CLU_027070_8_1_6; -.
DR InParanoid; P0AEB2; -.
DR OMA; QNTHFQT; -.
DR PhylomeDB; P0AEB2; -.
DR BioCyc; EcoCyc:EG10201-MON; -.
DR BioCyc; MetaCyc:EG10201-MON; -.
DR BRENDA; 3.4.16.4; 2026.
DR UniPathway; UPA00219; -.
DR EvolutionaryTrace; P0AEB2; -.
DR PRO; PR:P0AEB2; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:1990914; C:integral component of periplasmic side of plasma membrane; IDA:EcoCyc.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:EcoliWiki.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IDA:EcoCyc.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0008800; F:beta-lactamase activity; IDA:EcoCyc.
DR GO; GO:0004180; F:carboxypeptidase activity; IDA:EcoCyc.
DR GO; GO:0008658; F:penicillin binding; IDA:EcoCyc.
DR GO; GO:0009002; F:serine-type D-Ala-D-Ala carboxypeptidase activity; IDA:EcoliWiki.
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:0000270; P:peptidoglycan metabolic process; IDA:EcoCyc.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0008360; P:regulation of cell shape; IDA:EcoCyc.
DR Gene3D; 2.60.410.10; -; 1.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR InterPro; IPR015956; Peniciliin-bd_prot_C_sf.
DR InterPro; IPR018044; Peptidase_S11.
DR InterPro; IPR012907; Peptidase_S11_C.
DR InterPro; IPR037167; Peptidase_S11_C_sf.
DR InterPro; IPR001967; Peptidase_S11_N.
DR Pfam; PF07943; PBP5_C; 1.
DR Pfam; PF00768; Peptidase_S11; 1.
DR PRINTS; PR00725; DADACBPTASE1.
DR SMART; SM00936; PBP5_C; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
DR SUPFAM; SSF69189; SSF69189; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cell inner membrane; Cell membrane;
KW Cell shape; Cell wall biogenesis/degradation; Direct protein sequencing;
KW Hydrolase; Membrane; Peptidoglycan synthesis; Protease; Reference proteome;
KW Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:7042389"
FT CHAIN 30..403
FT /note="D-alanyl-D-alanine carboxypeptidase DacA"
FT /id="PRO_0000027231"
FT ACT_SITE 73
FT /note="Acyl-ester intermediate"
FT ACT_SITE 76
FT /note="Proton acceptor"
FT ACT_SITE 139
FT BINDING 242
FT /ligand="substrate"
FT VARIANT 134
FT /note="G -> D (in mutant dacA11191; inactive but still
FT binds penicillin. Blocked in the release of the bound
FT penicilloyl moiety; the mutant also fails to catalyze the
FT D-alanine carboxypeptidase reaction as the hydrolysis of
FT the acyl-enzyme formed with substrate is also blocked and
FT the acyl-enzyme accumulates)"
FT MUTAGEN 101..121
FT /note="Missing: Complete loss of enzyme activity. No effect
FT on penicillin binding."
FT /evidence="ECO:0000269|PubMed:14555648"
FT MUTAGEN 213
FT /note="K->R: Complete loss of enzyme activity. No effect on
FT penicillin binding."
FT /evidence="ECO:0000269|PubMed:1597468"
FT MUTAGEN 213
FT /note="K->X: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:1597468"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:3MZF"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 75..88
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 128..136
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 141..152
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 155..168
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 179..183
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 191..204
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 236..246
FT /evidence="ECO:0007829|PDB:3MZF"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 250..259
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 262..271
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 279..291
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 292..298
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 304..320
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 325..330
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 338..350
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 357..365
FT /evidence="ECO:0007829|PDB:3MZF"
FT STRAND 368..379
FT /evidence="ECO:0007829|PDB:3MZF"
FT HELIX 389..396
FT /evidence="ECO:0007829|PDB:6NTZ"
SQ SEQUENCE 403 AA; 44444 MW; 7FAAB8E98452FF22 CRC64;
MNTIFSARIM KRLALTTALC TAFISAAHAD DLNIKTMIPG VPQIDAESYI LIDYNSGKVL
AEQNADVRRD PASLTKMMTS YVIGQAMKAG KFKETDLVTI GNDAWATGNP VFKGSSLMFL
KPGMQVPVSQ LIRGINLQSG NDACVAMADF AAGSQDAFVG LMNSYVNALG LKNTHFQTVH
GLDADGQYSS ARDMALIGQA LIRDVPNEYS IYKEKEFTFN GIRQLNRNGL LWDNSLNVDG
IKTGHTDKAG YNLVASATEG QMRLISAVMG GRTFKGREAE SKKLLTWGFR FFETVNPLKV
GKEFASEPVW FGDSDRASLG VDKDVYLTIP RGRMKDLKAS YVLNSSELHA PLQKNQVVGT
INFQLDGKTI EQRPLVVLQE IPEGNFFGKI IDYIKLMFHH WFG
