PGDA_LISM4
ID PGDA_LISM4 Reviewed; 466 AA.
AC A0A0H3GDH9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Peptidoglycan-N-acetylglucosamine deacetylase PgdA {ECO:0000305};
DE Short=Peptidoglycan GlcNAc deacetylase {ECO:0000305};
DE EC=3.5.1.104 {ECO:0000250|UniProtKB:A0A3Q0NBH7};
DE AltName: Full=N-acetylglucosamine deacetylase Pgd {ECO:0000303|PubMed:21768286};
DE AltName: Full=Peptidoglycan N-deacetylase {ECO:0000303|PubMed:21768286};
DE Short=PG N-deacetylase {ECO:0000305};
DE AltName: Full=Petptidoglycan deacetylase {ECO:0000303|PubMed:25157076};
DE Short=PG deacetylase {ECO:0000305};
GN Name=pgdA {ECO:0000303|PubMed:25157076};
GN OrderedLocusNames=LMRG_00107 {ECO:0000312|EMBL:AEO05427.1};
OS Listeria monocytogenes serotype 1/2a (strain 10403S).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Listeriaceae; Listeria.
OX NCBI_TaxID=393133;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=10403S;
RG The Broad Institute Genome Sequencing Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Borowsky M., Borodovsky M., Young S.K., Zeng Q., Koehrsen M.,
RA Fitzgerald M., Wiedmann M., Swaminathan B., Lauer P., Portnoy D.,
RA Cossart P., Buchrieser C., Higgins D., Abouelleil A., Alvarado L.,
RA Arachchi H.M., Berlin A., Borenstein D., Brown A., Chapman S.B., Chen Z.,
RA Dunbar C.D., Engels R., Freedman E., Gearin G., Gellesch M., Goldberg J.,
RA Griggs A., Gujja S., Heilman E., Heiman D., Howarth C., Jen D., Larson L.,
RA Lui A., MacDonald J., Mehta T., Montmayeur A., Neiman D., Park D.,
RA Pearson M., Priest M., Richards J., Roberts A., Saif S., Shea T.,
RA Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J., Yandava C.,
RA Haas B., Nusbaum C., Birren B.;
RT "The genome sequence of Listeria monocytogenes strain 10403S.";
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=10403S {ECO:0000303|PubMed:21768286};
RX PubMed=21768286; DOI=10.1128/iai.00077-11;
RA Rae C.S., Geissler A., Adamson P.C., Portnoy D.A.;
RT "Mutations of the Listeria monocytogenes peptidoglycan N-deacetylase and O-
RT acetylase result in enhanced lysozyme sensitivity, bacteriolysis, and
RT hyperinduction of innate immune pathways.";
RL Infect. Immun. 79:3596-3606(2011).
RN [3]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=10403S {ECO:0000303|PubMed:25157076};
RX PubMed=25157076; DOI=10.1128/jb.02053-14;
RA Burke T.P., Loukitcheva A., Zemansky J., Wheeler R., Boneca I.G.,
RA Portnoy D.A.;
RT "Listeria monocytogenes is resistant to lysozyme through the regulation,
RT not the acquisition, of cell wall-modifying enzymes.";
RL J. Bacteriol. 196:3756-3767(2014).
CC -!- FUNCTION: Catalyzes the deacetylation of N-acetylglucosamine (GlcNAc)
CC residues in peptidoglycan (PG). Deacetylates also N-acetylated PG. Does
CC not deacetylate N-acetylmuramic acid (By similarity). Confers host
CC lysozyme resistance. Critical for virulence and escape from innate
CC immune response of the host (PubMed:21768286, PubMed:25157076).
CC Required for intracellular survival of bacteria in macrophages of the
CC host. Required for successful host colonization. Controls the
CC production of inflammatory mediators in the bone marrow derived
CC macrophages (BMMs) of the infected mouse (PubMed:21768286). Suppresses
CC Toll-like receptor 2 (TLR2)-dependent secretion of interleukin 6 (IL-6)
CC and interferon-beta (IFN-beta) in the macrophages of the infected
CC mouse. May decrease accessibility of pattern recognition receptors
CC (PRRs) such as nucleotide-binding oligomerization domain protein (NOD)
CC 1 of the host to the bacterial cell wall components (By similarity).
CC Protects cells from autolysis induced by lysozyme or by other
CC autolysis-inducing agents (By similarity).
CC {ECO:0000250|UniProtKB:A0A3Q0NBH7, ECO:0000250|UniProtKB:Q8Y9V5,
CC ECO:0000269|PubMed:21768286, ECO:0000269|PubMed:25157076}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=peptidoglycan-N-acetyl-D-glucosamine + H2O = peptidoglycan-D-
CC glucosamine + acetate.; EC=3.5.1.104;
CC Evidence={ECO:0000250|UniProtKB:A0A3Q0NBH7};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8DP63};
CC -!- SUBUNIT: Homodimer. Interacts (via transmembrane domain) with PbpA1
CC (via transmembrane domain); the interaction is important for the
CC peptidoglycan N-deacetylase function of this protein.
CC {ECO:0000250|UniProtKB:Q8Y9V5}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8Y9V5};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q8Y9V5,
CC ECO:0000255}; Extracellular side {ECO:0000250|UniProtKB:Q8Y9V5}.
CC Secreted, cell wall {ECO:0000250|UniProtKB:A0A3Q0NBH7}.
CC -!- INDUCTION: Transcriptionally up-regulated by response regulator DegU
CC and abundant non-coding RNA encoded by rli31.
CC {ECO:0000269|PubMed:25157076}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene have increased lysozyme
CC sensitivity (PubMed:21768286, PubMed:25157076). The growth is inhibited
CC by 100 ug/ml hen egg white lysozyme in broth culture and the optical
CC density of the culture is decreased, indicative of bacteriolysis.
CC Bacterial colony-forming unit (CFU) is decreased by 2 logs in the liver
CC and spleen of the intravenously Listeria-infected mouse. Mutant
CC bacterial cells have intracellular growth defects in the bone marrow
CC derived macrophages (BMMs) of the infected mouse, and increased
CC vacuolar and cytosolic expression of cytokines interleukin 12 (IL-12),
CC IL-1 beta and IFN-beta by the BMMs. Mutant cells undergo increased
CC bacteriolysis in the cytosol of the BMMs leading to IL-1 beta secretion
CC and AIM2 inflammasome-dependent pyroptosis of the infected host
CC macrophages via the PYCARD (ASC)-dependent pathway. Double pgdA/oatA
CC deletion mutants are more lysozyme sensitive than the single deletion
CC mutant of this gene. Both the single and double mutant phenotypes can
CC be rescued by lysozyme-deficient macrophages. The addition of
CC extracellular lysozyme to the lysozyme-deficient macrophages infected
CC by the mutants restores normal function of the BMMs (PubMed:21768286).
CC Exhibits attenuated virulence in mice. Killed within 30 min of
CC intravenous infection in the blood of infected mice. Is as resistant as
CC wild-type bacteria to beta-lactam antibiotics cefuroxime and penicillin
CC G, and to and cathelin-related antimicrobial peptide (CAMP) treatment.
CC Not killed by antimicrobial cationic peptides (PubMed:25157076).
CC {ECO:0000269|PubMed:21768286, ECO:0000269|PubMed:25157076}.
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DR EMBL; CP002002; AEO05427.1; -; Genomic_DNA.
DR RefSeq; WP_003733946.1; NC_017544.1.
DR AlphaFoldDB; A0A0H3GDH9; -.
DR SMR; A0A0H3GDH9; -.
DR EnsemblBacteria; AEO05427; AEO05427; LMRG_00107.
DR KEGG; lmt:LMRG_00107; -.
DR HOGENOM; CLU_037608_1_1_9; -.
DR OMA; DIHHESV; -.
DR Proteomes; UP000001288; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0009275; C:Gram-positive-bacterium-type cell wall; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0060241; F:lysozyme inhibitor activity; IMP:UniProtKB.
DR GO; GO:0050119; F:N-acetylglucosamine deacetylase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0001896; P:autolysis; ISS:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0042545; P:cell wall modification; ISS:UniProtKB.
DR GO; GO:0042783; P:evasion of host immune response; IMP:UniProtKB.
DR GO; GO:0042785; P:evasion of host immune response via regulation of host cytokine network; IMP:UniProtKB.
DR GO; GO:1903591; P:negative regulation of lysozyme activity; IMP:UniProtKB.
DR InterPro; IPR011330; Glyco_hydro/deAcase_b/a-brl.
DR InterPro; IPR002509; NODB_dom.
DR InterPro; IPR017219; Peptidoglycan_deacetylase.
DR Pfam; PF01522; Polysacc_deac_1; 1.
DR PIRSF; PIRSF037479; PG_GlcNAc_deacetylase; 1.
DR SUPFAM; SSF88713; SSF88713; 1.
DR PROSITE; PS51677; NODB; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell wall; Hydrolase; Membrane; Metal-binding; Secreted;
KW Transmembrane; Transmembrane helix; Virulence; Zinc.
FT CHAIN 1..466
FT /note="Peptidoglycan-N-acetylglucosamine deacetylase PgdA"
FT /id="PRO_0000452092"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..466
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 266..440
FT /note="NodB homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT ACT_SITE 273
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-1,
FT ECO:0000255|PROSITE-ProRule:PRU01014"
FT ACT_SITE 415
FT /note="Proton donor"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-1,
FT ECO:0000255|PROSITE-ProRule:PRU01014"
FT BINDING 274
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-3"
FT BINDING 324
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-3"
FT BINDING 328
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-3"
FT BINDING 365
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-2"
FT SITE 389
FT /note="Raises pKa of active site His"
FT /evidence="ECO:0000255|PIRSR:PIRSR037479-4"
SQ SEQUENCE 466 AA; 52496 MW; CB0595BF9A592E17 CRC64;
MKIRWIRLSL VAILIIAVVF IGVIGFQKYQ FSKSRNKVIM QMDRLMKDQD GGNFRRLDKK
ENGVEIISYI PKTTEKKDNE IIQKEIGKAT DAEVKKLNRD KETQGIIFYT YQKHRMAEQA
ISYKAVQSEY VKEGRTKFVL KDKKDICKNI VTDAETGALL TLGEVLIKSN QTKLNLKTAV
EEELIKTGDF SLKDVGNLGK IKSLVKWNQT DFEITNSEII LPVKIPGAPE PKKVKVKLAD
IASSVNKRYL PSSVKVPEVP KAKTNKRIAL TFDDGPSSSV TPGVLDTLKR HNVKATFFVL
GSSVIQNPGL VKRELEEGHQ VGSHSWDHPQ LTKQSTQEVY NQILKTQKAV FDQTGYFPTT
MRPPYGAVNK QVAEEIGLPI IQWSVDTEDW KYRNAGIVTK KVLAGATDGA IVLMHDIHKT
TAASLDTTLT KLKSQGYEFV TIDELYGEKL QIGKQYFDKT DSRMVK
