MEPA_ECOLI
ID MEPA_ECOLI Reviewed; 274 AA.
AC P0C0T5; P14007;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Penicillin-insensitive murein endopeptidase;
DE EC=3.4.24.- {ECO:0000269|PubMed:15292190};
DE AltName: Full=D-alanyl-D-alanine-endopeptidase;
DE Short=DD-endopeptidase;
DE Flags: Precursor;
GN Name=mepA; OrderedLocusNames=b2328, JW2325;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 20-30.
RC STRAIN=K12;
RX PubMed=2187143; DOI=10.1111/j.1365-2958.1990.tb00588.x;
RA Keck W., van Leeuwen A.M., Huber M., Goodell E.W.;
RT "Cloning and characterization of mepA, the structural gene of the
RT penicillin-insensitive murein endopeptidase from Escherichia coli.";
RL Mol. Microbiol. 4:209-219(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9205837; DOI=10.1093/dnares/4.2.91;
RA Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT its sequence features.";
RL DNA Res. 4:91-113(1997).
RN [3]
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 [4]
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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 20-274 AND IN COMPLEX WITH ZINC
RP ION, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MASS
RP SPECTROMETRY, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-113; ASP-120;
RP HIS-209 AND HIS-211, ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=15292190; DOI=10.1074/jbc.m406735200;
RA Marcyjaniak M., Odintsov S.G., Sabala I., Bochtler M.;
RT "Peptidoglycan amidase MepA is a LAS metallopeptidase.";
RL J. Biol. Chem. 279:43982-43989(2004).
CC -!- FUNCTION: Murein endopeptidase that cleaves the D-alanyl-meso-2,6-
CC diamino-pimelyl amide bond that connects peptidoglycan strands. Likely
CC plays a role in the removal of murein from the sacculus and could also
CC play a role in the integration of nascent murein strands into the
CC sacculus. {ECO:0000269|PubMed:15292190}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15292190};
CC Note=Binds 2 Zn(2+) ions per subunit. Zn(2+) ion 1 is bound in the
CC active site. Zn(2+) ion 2 is bound at the dimer interface by residues
CC from both subunits. {ECO:0000269|PubMed:15292190};
CC -!- ACTIVITY REGULATION: Inhibited by Zn(2+) at 10 mM and by metal
CC chelating agents EDTA and 1,10-phenanthroline.
CC {ECO:0000269|PubMed:15292190}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5-8. {ECO:0000269|PubMed:15292190};
CC -!- SUBUNIT: Dimer. {ECO:0000269|PubMed:15292190}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000305|PubMed:15292190}.
CC -!- MASS SPECTROMETRY: Mass=28295; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:15292190};
CC -!- MISCELLANEOUS: In E.coli there are three murein endopeptidases: two are
CC penicillin sensitive (DacB and PbpG), the other (MepA) not.
CC {ECO:0000269|PubMed:15292190}.
CC -!- SIMILARITY: Belongs to the peptidase M74 family. {ECO:0000305}.
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DR EMBL; X16909; CAA34782.1; -; mRNA.
DR EMBL; U00096; AAC75388.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA16184.1; -; Genomic_DNA.
DR PIR; S08345; S08345.
DR RefSeq; NP_416831.1; NC_000913.3.
DR RefSeq; WP_001043825.1; NZ_LN832404.1.
DR PDB; 1TZP; X-ray; 1.40 A; A/B=20-274.
DR PDB; 1U10; X-ray; 2.40 A; A/B/C/D/E/F=20-274.
DR PDBsum; 1TZP; -.
DR PDBsum; 1U10; -.
DR AlphaFoldDB; P0C0T5; -.
DR SMR; P0C0T5; -.
DR BioGRID; 4259647; 321.
DR IntAct; P0C0T5; 2.
DR STRING; 511145.b2328; -.
DR DrugBank; DB01955; 1,4-Butanediol.
DR MEROPS; M74.001; -.
DR PaxDb; P0C0T5; -.
DR PRIDE; P0C0T5; -.
DR EnsemblBacteria; AAC75388; AAC75388; b2328.
DR EnsemblBacteria; BAA16184; BAA16184; BAA16184.
DR GeneID; 58388052; -.
DR GeneID; 946812; -.
DR KEGG; ecj:JW2325; -.
DR KEGG; eco:b2328; -.
DR PATRIC; fig|1411691.4.peg.4404; -.
DR EchoBASE; EB0575; -.
DR eggNOG; COG3770; Bacteria.
DR HOGENOM; CLU_052496_0_0_6; -.
DR InParanoid; P0C0T5; -.
DR OMA; VRPWWGH; -.
DR PhylomeDB; P0C0T5; -.
DR BioCyc; EcoCyc:EG10580-MON; -.
DR BioCyc; MetaCyc:EG10580-MON; -.
DR EvolutionaryTrace; P0C0T5; -.
DR PRO; PR:P0C0T5; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IEA:InterPro.
DR GO; GO:0004175; F:endopeptidase activity; IMP:EcoCyc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008233; F:peptidase activity; IDA:EcoCyc.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IDA:EcoCyc.
DR GO; GO:0000270; P:peptidoglycan metabolic process; IDA:EcoCyc.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1380.10; -; 1.
DR HAMAP; MF_01623; MepA; 1.
DR InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf.
DR InterPro; IPR005073; Peptidase_M74.
DR Pfam; PF03411; Peptidase_M74; 1.
DR PIRSF; PIRSF018455; MepA; 1.
DR SUPFAM; SSF55166; SSF55166; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Metal-binding; Metalloprotease; Periplasm; Protease; Reference proteome;
KW Signal; Zinc.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:2187143"
FT CHAIN 20..274
FT /note="Penicillin-insensitive murein endopeptidase"
FT /id="PRO_0000028520"
FT REGION 228..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15292190"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15292190"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15292190"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15292190"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15292190"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15292190"
FT DISULFID 44..265
FT /evidence="ECO:0000269|PubMed:15292190"
FT DISULFID 187..235
FT /evidence="ECO:0000269|PubMed:15292190"
FT DISULFID 216..223
FT /evidence="ECO:0000269|PubMed:15292190"
FT MUTAGEN 113
FT /note="H->A: Strongly reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:15292190"
FT MUTAGEN 120
FT /note="D->A: Strongly reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:15292190"
FT MUTAGEN 209
FT /note="H->A: Strongly reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:15292190"
FT MUTAGEN 211
FT /note="H->A: Strongly reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:15292190"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1U10"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 132..136
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1TZP"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 158..169
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 180..189
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:1TZP"
FT STRAND 207..214
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 237..241
FT /evidence="ECO:0007829|PDB:1TZP"
FT HELIX 263..270
FT /evidence="ECO:0007829|PDB:1TZP"
SQ SEQUENCE 274 AA; 30137 MW; EF91AFD4B381019A CRC64;
MNKTAIALLA LLASSASLAA TPWQKITQPV PGSAQSIGSF SNGCIVGADT LPIQSEHYQV
MRTDQRRYFG HPDLVMFIQR LSSQVSNLGM GTVLIGDMGM PAGGRFNGGH ASHQTGLDVD
IFLQLPKTRW TSAQLLRPQA LDLVSRDGKH VVSTLWKPEI FSLIKLAAQD KDVTRIFVNP
AIKQQLCLDA GTDRDWLRKV RPWFQHRAHM HVRLRCPADS LECEDQPLPP SGDGCGAELQ
SWFEPPKPGT TKPEKKTPPP LPPSCQALLD EHVI
