PGDA_STRR6
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 03-AUG-2022, entry version 112.
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; Firmicutes; 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}.
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; AE007317; AAL00137.1; -; Genomic_DNA.
DR PIR; D98038; D98038.
DR RefSeq; NP_358926.1; NC_003098.1.
DR RefSeq; WP_001854799.1; NC_003098.1.
DR PDB; 2C1G; X-ray; 1.75 A; A=38-463.
DR PDB; 2C1I; X-ray; 1.35 A; A=38-463.
DR PDBsum; 2C1G; -.
DR PDBsum; 2C1I; -.
DR AlphaFoldDB; Q8DP63; -.
DR SMR; Q8DP63; -.
DR STRING; 171101.spr1333; -.
DR BindingDB; Q8DP63; -.
DR ChEMBL; CHEMBL4295617; -.
DR PRIDE; Q8DP63; -.
DR EnsemblBacteria; AAL00137; AAL00137; spr1333.
DR GeneID; 60232726; -.
DR KEGG; spr:spr1333; -.
DR PATRIC; fig|171101.6.peg.1445; -.
DR eggNOG; COG0726; Bacteria.
DR HOGENOM; CLU_037608_1_1_9; -.
DR OMA; FFMMGSK; -.
DR BRENDA; 3.5.1.104; 1960.
DR EvolutionaryTrace; Q8DP63; -.
DR Proteomes; UP000000586; Chromosome.
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; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042545; P:cell wall modification; IDA:UniProtKB.
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 Pfam; PF18627; PgdA_N; 1.
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 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
