PGDA_LISMO
ID PGDA_LISMO Reviewed; 466 AA.
AC Q8Y9V5;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 98.
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=Peptidoglycan N-deacetylase {ECO:0000303|PubMed:17215377};
DE Short=PG N-deacetylase {ECO:0000303|PubMed:17215377};
DE AltName: Full=Petptidoglycan deacetylase {ECO:0000303|PubMed:17215377};
DE Short=PG deacetylase {ECO:0000303|PubMed:17215377};
GN Name=pgdA {ECO:0000303|PubMed:17215377, ECO:0000303|PubMed:21844299,
GN ECO:0000303|PubMed:29215169};
GN OrderedLocusNames=lmo0415 {ECO:0000303|PubMed:17215377,
GN ECO:0000312|EMBL:CAC98494.1};
OS Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Listeriaceae; Listeria.
OX NCBI_TaxID=169963;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-679 / EGD-e;
RX PubMed=11679669; DOI=10.1126/science.1063447;
RA Glaser P., Frangeul L., Buchrieser C., Rusniok C., Amend A., Baquero F.,
RA Berche P., Bloecker H., Brandt P., Chakraborty T., Charbit A.,
RA Chetouani F., Couve E., de Daruvar A., Dehoux P., Domann E.,
RA Dominguez-Bernal G., Duchaud E., Durant L., Dussurget O., Entian K.-D.,
RA Fsihi H., Garcia-del Portillo F., Garrido P., Gautier L., Goebel W.,
RA Gomez-Lopez N., Hain T., Hauf J., Jackson D., Jones L.-M., Kaerst U.,
RA Kreft J., Kuhn M., Kunst F., Kurapkat G., Madueno E., Maitournam A.,
RA Mata Vicente J., Ng E., Nedjari H., Nordsiek G., Novella S., de Pablos B.,
RA Perez-Diaz J.-C., Purcell R., Remmel B., Rose M., Schlueter T., Simoes N.,
RA Tierrez A., Vazquez-Boland J.-A., Voss H., Wehland J., Cossart P.;
RT "Comparative genomics of Listeria species.";
RL Science 294:849-852(2001).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-679 / EGD-e {ECO:0000303|PubMed:17215377};
RX PubMed=17215377; DOI=10.1073/pnas.0609672104;
RA Boneca I.G., Dussurget O., Cabanes D., Nahori M.A., Sousa S., Lecuit M.,
RA Psylinakis E., Bouriotis V., Hugot J.P., Giovannini M., Coyle A.,
RA Bertin J., Namane A., Rousselle J.C., Cayet N., Prevost M.C., Balloy V.,
RA Chignard M., Philpott D.J., Cossart P., Girardin S.E.;
RT "A critical role for peptidoglycan N-deacetylation in Listeria evasion from
RT the host innate immune system.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:997-1002(2007).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-679 / EGD-e {ECO:0000303|PubMed:21844299};
RX PubMed=21844299; DOI=10.1093/infdis/jir396;
RA Aubry C., Goulard C., Nahori M.A., Cayet N., Decalf J., Sachse M.,
RA Boneca I.G., Cossart P., Dussurget O.;
RT "OatA, a peptidoglycan O-acetyltransferase involved in Listeria
RT monocytogenes immune escape, is critical for virulence.";
RL J. Infect. Dis. 204:731-740(2011).
RN [4]
RP SUBUNIT, INTERACTION WITH PBPA1, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF TRP-5; ARG-7; LEU-8; ILE-15; VAL-19 AND
RP 29-TYR--LYS-466.
RC STRAIN=ATCC BAA-679 / EGD-e {ECO:0000303|PubMed:29215169};
RX PubMed=29215169; DOI=10.1111/mmi.13893;
RA Rismondo J., Wamp S., Aldridge C., Vollmer W., Halbedel S.;
RT "Stimulation of PgdA-dependent peptidoglycan N-deacetylation by GpsB-PBP A1
RT in Listeria monocytogenes.";
RL Mol. Microbiol. 107:472-487(2018).
CC -!- FUNCTION: Catalyzes the deacetylation of N-acetylglucosamine (GlcNAc)
CC residues in peptidoglycan (PG) (By similarity). Deacetylates also N-
CC acetylated PG (PubMed:17215377). Does not deacetylate N-acetylmuramic
CC acid (By similarity). Confers host lysozyme resistance
CC (PubMed:17215377, PubMed:29215169). Critical for virulence and escape
CC from innate immune response of the host. Required for intracellular
CC survival of bacteria in macrophages of the host (PubMed:17215377).
CC Required for successful host colonization (PubMed:17215377,
CC PubMed:21844299). Controls the production of inflammatory mediators in
CC the bone marrow derived macrophages (BMMs) of the infected mouse (By
CC similarity). Suppresses Toll-like receptor 2 (TLR2)-dependent secretion
CC of interleukin 6 (IL-6) and interferon-beta (IFN-beta) in the
CC macrophages of the infected mouse. May decrease accessibility of
CC pattern recognition receptors (PRRs) such as nucleotide-binding
CC oligomerization domain protein (NOD) 1 of the host to the bacterial
CC cell wall components (PubMed:17215377). Protects cells from autolysis
CC induced by lysozyme or by other autolysis-inducing agents (By
CC similarity). {ECO:0000250|UniProtKB:A0A0H3GDH9,
CC ECO:0000250|UniProtKB:A0A3Q0NBH7, ECO:0000269|PubMed:17215377,
CC ECO:0000269|PubMed:21844299}.
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:0000269|PubMed:29215169}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:29215169};
CC Single-pass membrane protein {ECO:0000255,
CC ECO:0000305|PubMed:29215169}; Extracellular side
CC {ECO:0000305|PubMed:29215169}. Secreted, cell wall
CC {ECO:0000250|UniProtKB:A0A3Q0NBH7}.
CC -!- INDUCTION: Transcriptionally up-regulated by response regulator DegU
CC and abundant non-coding RNA encoded by rli31.
CC {ECO:0000250|UniProtKB:A0A0H3GDH9}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene completely lack the N-
CC deacetylated muropeptides characteristic of the wild-type. Extremely
CC sensitive to lysozyme in stationary phase as shown by five-log decrease
CC in viability compared with the wild-type. Not sensitive to human serum
CC amidase. Impaired survival and multiplication in Listeria-infected
CC murine macrophage-like (RAW264.7) cells, mouse peritoneal-elicited
CC macrophages (PEM) and bone marrow-derived macrophages (BMDM). Impaired
CC escape from phagosomes of macrophages and rapidly killed within
CC macrophage vacuoles of the infected mouse. Impaired in surviving at
CC early stages of infection in intestinal lumen, intestine and mesenteric
CC lymph nodes of orally infected human E-cadherin transgenic mice, which
CC are permissive to Listeria oral infection. Severely attenuated in
CC virulence at later stages of infection in intravenously infected mouse
CC shown by lower bacterial counts compared to wild-type in both liver and
CC spleen of the infected mouse. Induces interleukin 6 (IL-6) and a
CC massive IFN-beta production in RAW264.7 and PEM cells of the infected
CC mouse in a manner that is dependent on Toll-like receptor 2 (TLR2) and
CC also affected by nucleotide-binding oligomerization domain protein
CC (NOD) 1 (PubMed:17215377). Not detected in bloodstream, and strongly
CC impaired colonization in liver and spleen of mouse injected
CC intravenously by Listeria compared to wild-type. Secretion of cytokines
CC interleukin 2 (IL-2), IL-6, IL-12 and IL-5, chemokines CCL2 and CXCL9,
CC or CCL3 (macrophage inflammatory protein-1alpha) by the liver cells of
CC the infected mouse is similar to wild-type. The virulence of a double
CC oatA/pgdA deletion mutant is more reduced than that of either single
CC mutant as detected by lack of colonization in the bloodstream, liver
CC and spleen of infected mouse 24 hours postinfection (PubMed:21844299).
CC Massive reduction of resistance against lysozyme compared to wild-type.
CC Most mutant cells are lysed within the first 30 min of lysozyme
CC exposure (PubMed:29215169). {ECO:0000269|PubMed:17215377,
CC ECO:0000269|PubMed:21844299, ECO:0000269|PubMed:29215169}.
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DR EMBL; AL591975; CAC98494.1; -; Genomic_DNA.
DR PIR; AH1126; AH1126.
DR RefSeq; NP_463944.1; NC_003210.1.
DR RefSeq; WP_003733946.1; NZ_CP023861.1.
DR AlphaFoldDB; Q8Y9V5; -.
DR SMR; Q8Y9V5; -.
DR STRING; 169963.lmo0415; -.
DR PaxDb; Q8Y9V5; -.
DR EnsemblBacteria; CAC98494; CAC98494; CAC98494.
DR GeneID; 987823; -.
DR KEGG; lmo:lmo0415; -.
DR PATRIC; fig|169963.11.peg.428; -.
DR eggNOG; COG0726; Bacteria.
DR HOGENOM; CLU_037608_1_1_9; -.
DR OMA; DIHHESV; -.
DR PhylomeDB; Q8Y9V5; -.
DR BioCyc; LMON169963:LMO0415-MON; -.
DR PHI-base; PHI:4689; -.
DR Proteomes; UP000000817; Chromosome.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0009275; C:Gram-positive-bacterium-type cell wall; IMP:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; NAS:UniProtKB.
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; IMP: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; 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 1: Evidence at protein level;
KW Cell membrane; Cell wall; Hydrolase; Membrane; Metal-binding;
KW Reference proteome; Secreted; Transmembrane; Transmembrane helix;
KW Virulence; Zinc.
FT CHAIN 1..466
FT /note="Peptidoglycan-N-acetylglucosamine deacetylase PgdA"
FT /id="PRO_0000452093"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29215169"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..466
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:29215169"
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"
FT MUTAGEN 5
FT /note="W->A: Loss of homodimerization, but interacts with
FT full-length PbpA1; when associated with 29-Y--K-466.
FT Reduced resistance against lysozyme."
FT /evidence="ECO:0000269|PubMed:29215169"
FT MUTAGEN 7
FT /note="R->A: Loss of interaction with full-length PbpA1,
FT but homodimerizes; when associated with 29-Y--K-466.
FT Reduced resistance against lysozyme."
FT /evidence="ECO:0000269|PubMed:29215169"
FT MUTAGEN 8
FT /note="L->A: Loss of homodimerization, but interacts with
FT full-length PbpA1; when associated with 29-Y--K-466.
FT Reduced resistance against lysozyme."
FT /evidence="ECO:0000269|PubMed:29215169"
FT MUTAGEN 15
FT /note="I->A: Loss of interaction with full-length PbpA1,
FT but homodimerizes; when associated with 29-Y--K-466.
FT Reduced resistance against lysozyme."
FT /evidence="ECO:0000269|PubMed:29215169"
FT MUTAGEN 19
FT /note="V->A: Loss of interaction with full-length PbpA1,
FT but homodimerizes; when associated with 29-Y--K-466. No
FT effect in resistance against lysozyme."
FT /evidence="ECO:0000269|PubMed:29215169"
FT MUTAGEN 29..466
FT /note="Missing: Interacts with full-length PbpA1 and with
FT truncated PbpA1 consisting of only residues 1-91 of the N-
FT terminus which includes its transmembrane domain."
FT /evidence="ECO:0000269|PubMed:29215169"
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
