ID   PGDA_STRR6              Reviewed;         463 AA.
AC   Q8DP63;
DT   13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   02-SEP-2026, entry version 127.
DE   RecName: Full=Peptidoglycan-N-acetylglucosamine deacetylase {ECO:0000303|PubMed:10781617};
DE            Short=Peptidoglycan GlcNAc deacetylase {ECO:0000305};
DE            EC=3.5.1.104 {ECO:0000269|PubMed:10781617, ECO:0000269|PubMed:16221761};
DE   AltName: Full=Peptidoglycan N-deacetylase {ECO:0000303|PubMed:16221761};
DE            Short=PG N-deacetylase {ECO:0000305};
GN   Name=pgdA {ECO:0000303|PubMed:10781617}; OrderedLocusNames=spr1333;
OS   Streptococcus pneumoniae (strain ATCC BAA-255 / R6).
OC   Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=171101;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-255 / R6;
RX   PubMed=11544234; DOI=10.1128/jb.183.19.5709-5717.2001;
RA   Hoskins J., Alborn W.E. Jr., Arnold J., Blaszczak L.C., Burgett S.,
RA   DeHoff B.S., Estrem S.T., Fritz L., Fu D.-J., Fuller W., Geringer C.,
RA   Gilmour R., Glass J.S., Khoja H., Kraft A.R., Lagace R.E., LeBlanc D.J.,
RA   Lee L.N., Lefkowitz E.J., Lu J., Matsushima P., McAhren S.M., McHenney M.,
RA   McLeaster K., Mundy C.W., Nicas T.I., Norris F.H., O'Gara M., Peery R.B.,
RA   Robertson G.T., Rockey P., Sun P.-M., Winkler M.E., Yang Y.,
RA   Young-Bellido M., Zhao G., Zook C.A., Baltz R.H., Jaskunas S.R.,
RA   Rosteck P.R. Jr., Skatrud P.L., Glass J.I.;
RT   "Genome of the bacterium Streptococcus pneumoniae strain R6.";
RL   J. Bacteriol. 183:5709-5717(2001).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, GENE NAME, AND DISRUPTION PHENOTYPE.
RC   STRAIN=R36A;
RX   PubMed=10781617; DOI=10.1074/jbc.m910189199;
RA   Vollmer W., Tomasz A.;
RT   "The pgdA gene encodes for a peptidoglycan N-acetylglucosamine deacetylase
RT   in Streptococcus pneumoniae.";
RL   J. Biol. Chem. 275:20496-20501(2000).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=R36A;
RX   PubMed=12438406; DOI=10.1128/iai.70.12.7176-7178.2002;
RA   Vollmer W., Tomasz A.;
RT   "Peptidoglycan N-acetylglucosamine deacetylase, a putative virulence factor
RT   in Streptococcus pneumoniae.";
RL   Infect. Immun. 70:7176-7178(2002).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 38-463 OF WILD-TYPE AND MUTANT
RP   ASN-275 IN COMPLEX WITH ACETATE PRODUCT AND ZINC, FUNCTION, CATALYTIC
RP   ACTIVITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP   REACTION MECHANISM, ACTIVE SITE, AND MUTAGENESIS OF ASP-275; HIS-326;
RP   ARG-364; ASP-391 AND HIS-417.
RX   PubMed=16221761; DOI=10.1073/pnas.0504339102;
RA   Blair D.E., Schuttelkopf A.W., MacRae J.I., van Aalten D.M.;
RT   "Structure and metal-dependent mechanism of peptidoglycan deacetylase, a
RT   streptococcal virulence factor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:15429-15434(2005).
CC   -!- FUNCTION: Catalyzes the deacetylation of N-acetylglucosamine (GlcNAc)
CC       residues in peptidoglycan, a modification that confers host lysozyme
CC       resistance and contributes to pneumococcal virulence.
CC       {ECO:0000269|PubMed:10781617, ECO:0000269|PubMed:12438406,
CC       ECO:0000269|PubMed:16221761}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=peptidoglycan-N-acetyl-D-glucosamine + H2O = peptidoglycan-D-
CC         glucosamine + acetate.; EC=3.5.1.104;
CC         Evidence={ECO:0000269|PubMed:10781617, ECO:0000269|PubMed:16221761};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:16221761};
CC       Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC         Evidence={ECO:0000269|PubMed:16221761};
CC       Note=Zn(2+). Although displays higher activity with Co(2+) than with
CC       Zn(2+) in vitro, bioavailability may well limit this enzyme to be zinc-
CC       dependent. {ECO:0000269|PubMed:16221761};
CC   -!- ACTIVITY REGULATION: Enzymatic activity is inhibited by EDTA in vitro.
CC       {ECO:0000269|PubMed:16221761}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3.8 mM for GlcNAc3 {ECO:0000269|PubMed:16221761};
CC         Note=kcat is 0.55 sec(-1) with GlcNAc3 as substrate.
CC         {ECO:0000269|PubMed:16221761};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene produce fully N-
CC       acetylated glycan, become hypersensitive to exogenous lysozyme in the
CC       stationary phase of growth, and show reduced virulence in the
CC       intraperitoneal mouse model. {ECO:0000269|PubMed:10781617,
CC       ECO:0000269|PubMed:12438406}.
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DR   EMBL; AE007317; AAL00137.1; -; Genomic_DNA.
DR   PIR; D98038; D98038.
DR   RefSeq; WP_001854799.1; NC_003098.1.
DR   PDB; 2C1G; X-ray; 1.75 A; A=33-463.
DR   PDB; 2C1I; X-ray; 1.35 A; A=33-463.
DR   AlphaFoldDB; Q8DP63; -.
DR   SMR; Q8DP63; -.
DR   STRING; 171101.spr1333; -.
DR   BindingDB; Q8DP63; -.
DR   ChEMBL; CHEMBL4295617; -.
DR   PaxDb; 171101-spr1333; -.
DR   KEGG; spr:spr1333; -.
DR   PATRIC; fig|171101.6.peg.1445; -.
DR   eggNOG; COG0726; Bacteria.
DR   HOGENOM; CLU_037608_1_1_9; -.
DR   BRENDA; 3.5.1.104; 1960.
DR   EvolutionaryTrace; Q8DP63; -.
DR   Proteomes; UP000000586; Chromosome.
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; IDA:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0042545; P:cell wall modification; IDA:UniProtKB.
DR   CDD; cd10947; CE4_SpPgdA_BsYjeA_like; 1.
DR   Gene3D; 3.30.565.50; -; 1.
DR   Gene3D; 3.90.640.30; -; 1.
DR   Gene3D; 3.20.20.370; Glycoside hydrolase/deacetylase; 1.
DR   InterPro; IPR054897; GlcNAc_deacetylase.
DR   InterPro; IPR011330; Glyco_hydro/deAcase_b/a-brl.
DR   InterPro; IPR002509; NODB_dom.
DR   InterPro; IPR017219; Peptidoglycan_deacetylase.
DR   InterPro; IPR040802; PgdA_N.
DR   InterPro; IPR050248; Polysacc_deacetylase_ArnD.
DR   NCBIfam; NF045820; PgAcgDacpgdA_Strep; 1.
DR   PANTHER; PTHR10587:SF133; CHITIN DEACETYLASE 1-RELATED; 1.
DR   PANTHER; PTHR10587; GLYCOSYL TRANSFERASE-RELATED; 1.
DR   Pfam; PF18627; PgdA_N; 1.
DR   Pfam; PF01522; Polysacc_deac_1; 1.
DR   PIRSF; PIRSF037479; PG_GlcNAc_deacetylase; 1.
DR   SUPFAM; SSF88713; Glycoside hydrolase/deacetylase; 1.
DR   SUPFAM; SSF144015; Peptidoglycan deacetylase N-terminal noncatalytic region; 1.
DR   PROSITE; PS51677; NODB; 1.
DR   PDBsum; 2C1G; -.
DR   PDBsum; 2C1I; -.
PE   1: Evidence at protein level;
KW   3D-structure; Carbohydrate metabolism; Cell membrane; Cobalt; Hydrolase;
KW   Membrane; Metal-binding; Reference proteome; Transmembrane;
KW   Transmembrane helix; Virulence; Zinc.
FT   CHAIN           1..463
FT                   /note="Peptidoglycan-N-acetylglucosamine deacetylase"
FT                   /id="PRO_0000424440"
FT   TRANSMEM        18..38
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          268..442
FT                   /note="NodB homology"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01014"
FT   ACT_SITE        275
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   ACT_SITE        417
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   BINDING         276
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   BINDING         326
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   BINDING         330
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   BINDING         367
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   SITE            391
FT                   /note="Raises pKa of active site His"
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   MUTAGEN         275
FT                   /note="D->N: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   MUTAGEN         326
FT                   /note="H->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   MUTAGEN         364
FT                   /note="R->S: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   MUTAGEN         391
FT                   /note="D->N: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   MUTAGEN         417
FT                   /note="H->S: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:16221761"
FT   HELIX           47..61
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          65..72
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          75..84
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           90..102
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          110..119
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          125..135
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          138..141
FT                   /evidence="ECO:0007829|PDB:2C1G"
FT   STRAND          144..156
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           164..167
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           171..184
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           208..210
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          213..216
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          219..222
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          234..237
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           238..244
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           247..249
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           252..265
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          269..276
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   TURN            280..282
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           283..292
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          298..301
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           303..305
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   TURN            306..308
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           310..318
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          322..325
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           333..335
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           338..356
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           366..368
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           372..376
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          381..383
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          386..388
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           391..394
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           397..407
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          412..417
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           421..436
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           444..448
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   HELIX           449..451
FT                   /evidence="ECO:0007829|PDB:2C1I"
FT   STRAND          457..461
FT                   /evidence="ECO:0007829|PDB:2C1I"
SQ   SEQUENCE   463 AA;  52675 MW;  12E1935E66521EDE CRC64;
     MNKSRLGRGR HGKTRHVLLA LIGILAISIC LLGGFIAFKI YQQKSFEQKI ESLKKEKDDQ
     LSEGNQKEHF RQGQAEVIAY YPLQGEKVIS SVRELINQDV KDKLESKDNL VFYYTEQEES
     GLKGVVNRNV TKQIYDLVAF KIEETEKTSL GKVHLTEDGQ PFTLDQLFSD ASKAKEQLIK
     ELTSFIEDKK IEQDQSEQIV KNFSDQDLSA WNFDYKDSQI ILYPSPVVEN LEEIALPVSA
     FFDVIQSSYL LEKDAALYQS YFDKKHQKVV ALTFDDGPNP ATTPQVLETL AKYDIKATFF
     VLGKNVSGNE DLVKRIKSEG HVVGNHSWSH PILSQLSLDE AKKQITDTED VLTKVLGSSS
     KLMRPPYGAI TDDIRNSLDL SFIMWDVDSL DWKSKNEASI LTEIQHQVAN GSIVLMHDIH
     SPTVNALPRV IEYLKNQGYT FVTIPEMLNT RLKAHELYYS RDE
//