PBP2A_STRP2
ID PBP2A_STRP2 Reviewed; 731 AA.
AC A0A0H2ZMF9;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Penicillin-binding protein 2a {ECO:0000305};
DE Short=PBP2a {ECO:0000303|PubMed:29487215};
DE AltName: Full=Cell wall synthase PBP2a {ECO:0000303|PubMed:29487215};
DE Includes:
DE RecName: Full=Penicillin-insensitive transglycosylase {ECO:0000305};
DE EC=2.4.1.129 {ECO:0000250|UniProtKB:Q8DNB6};
DE AltName: Full=Peptidoglycan TGase {ECO:0000305};
DE AltName: Full=Peptidoglycan glycosyltransferase {ECO:0000305};
DE Includes:
DE RecName: Full=Penicillin-sensitive transpeptidase {ECO:0000305};
DE EC=3.4.16.4 {ECO:0000250|UniProtKB:Q8DNB6};
DE AltName: Full=DD-transpeptidase {ECO:0000305};
GN Name=pbp2a {ECO:0000312|EMBL:ABJ54295.1};
GN OrderedLocusNames=SPD_1821 {ECO:0000312|EMBL:ABJ54295.1};
OS Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=373153 {ECO:0000312|EMBL:ABJ54295.1};
RN [1] {ECO:0000312|EMBL:ABJ54295.1, ECO:0000312|Proteomes:UP000001452}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=D39 / NCTC 7466 {ECO:0000312|Proteomes:UP000001452};
RX PubMed=17041037; DOI=10.1128/jb.01148-06;
RA Lanie J.A., Ng W.-L., Kazmierczak K.M., Andrzejewski T.M., Davidsen T.M.,
RA Wayne K.J., Tettelin H., Glass J.I., Winkler M.E.;
RT "Genome sequence of Avery's virulent serotype 2 strain D39 of Streptococcus
RT pneumoniae and comparison with that of unencapsulated laboratory strain
RT R6.";
RL J. Bacteriol. 189:38-51(2007).
RN [2]
RP INTERACTION WITH MACP, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=D39 / NCTC 7466 {ECO:0000303|PubMed:29487215};
RX PubMed=29487215; DOI=10.1073/pnas.1715218115;
RA Fenton A.K., Manuse S., Flores-Kim J., Garcia P.S., Mercy C.,
RA Grangeasse C., Bernhardt T.G., Rudner D.Z.;
RT "Phosphorylation-dependent activation of the cell wall synthase PBP2a in
RT Streptococcus pneumoniae by MacP.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:2812-2817(2018).
CC -!- FUNCTION: Cell wall formation. Synthesis of cross-linked peptidoglycan
CC (PG) from the lipid intermediates (By similarity). Binds dansylated
CC lipid II and catalyzes the polymerization of glycan chains. Hydrolyzes
CC S2d (N-benzoyl-D-alanylmercaptoacetic acid) molecule, a synthetic
CC thiolester analog of cell wall stem peptide. Active against bocillin, a
CC fluorescent penicillin. No transpeptidase activity with non-fluorescent
CC lysine-containing lipid II as substrate (By similarity).
CC {ECO:0000250|UniProtKB:P02918, ECO:0000250|UniProtKB:Q8DNB6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: (Ac)2-L-Lys-D-Ala-|-D-Ala. Also
CC transpeptidation of peptidyl-alanyl moieties that are N-acyl
CC substituents of D-alanine.; EC=3.4.16.4;
CC Evidence={ECO:0000250|UniProtKB:Q8DNB6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-
CC Ala)](n)-di-trans,octa-cis-undecaprenyl diphosphate + beta-D-GlcNAc-
CC (1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-
CC cis-undecaprenyl diphosphate = [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-
CC D-Glu-L-Lys-D-Ala-D-Ala)](n+1)-di-trans-octa-cis-undecaprenyl
CC diphosphate + di-trans,octa-cis-undecaprenyl diphosphate + H(+);
CC Xref=Rhea:RHEA:23708, Rhea:RHEA-COMP:9602, Rhea:RHEA-COMP:9603,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58405, ChEBI:CHEBI:60033,
CC ChEBI:CHEBI:78435; EC=2.4.1.129;
CC Evidence={ECO:0000250|UniProtKB:Q8DNB6};
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. May also form higher order oligomers. Self-
CC association may depend on its transmembrane and/or cytoplasmic regions
CC (By similarity). Interacts with MacP; interaction is required for the
CC function of this protein (PubMed:29487215).
CC {ECO:0000250|UniProtKB:Q8DNB6, ECO:0000269|PubMed:29487215}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29487215};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q8DNB6}.
CC Secreted, cell wall {ECO:0000305}. Note=Localizes to sites of new
CC peptidoglycan (PG) synthesis at midcell independently of MacP.
CC {ECO:0000269|PubMed:29487215}.
CC -!- DOMAIN: Has a penicillin-insensitive
CC transglycosylase/glycosyltransferase (GT) N-terminal domain (formation
CC of linear glycan strands) and a penicillin-sensitive transpeptidase C-
CC terminal domain (cross-linking of the peptide subunits). Transmembrane
CC signal-anchor is required for the synthesis of longer, 20-30
CC disaccharide units containing, glycan chains.
CC {ECO:0000250|UniProtKB:Q8DNB6}.
CC -!- DISRUPTION PHENOTYPE: Deletion of this gene with concomitant depletion
CC of PBP1a leads to progressive reduction in cell size before ultimate
CC lysis. Cell wall synthesis is also dramatically reduced in these cells.
CC {ECO:0000269|PubMed:29487215}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC glycosyltransferase 51 family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the transpeptidase
CC family. {ECO:0000305}.
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DR EMBL; CP000410; ABJ54295.1; -; Genomic_DNA.
DR RefSeq; WP_000762624.1; NC_008533.2.
DR AlphaFoldDB; A0A0H2ZMF9; -.
DR SMR; A0A0H2ZMF9; -.
DR STRING; 373153.SPD_1821; -.
DR EnsemblBacteria; ABJ54295; ABJ54295; SPD_1821.
DR GeneID; 60233563; -.
DR KEGG; spd:SPD_1821; -.
DR eggNOG; COG0744; Bacteria.
DR HOGENOM; CLU_006354_2_2_9; -.
DR OMA; AVQMPYI; -.
DR OrthoDB; 652304at2; -.
DR BioCyc; SPNE373153:G1G6V-1967-MON; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001452; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
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:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008658; F:penicillin binding; IEA:InterPro.
DR GO; GO:0008955; F:peptidoglycan glycosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0009002; F:serine-type D-Ala-D-Ala carboxypeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 1.10.3810.10; -; 1.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR InterPro; IPR001264; Glyco_trans_51.
DR InterPro; IPR023346; Lysozyme-like_dom_sf.
DR InterPro; IPR036950; PBP_transglycosylase.
DR InterPro; IPR001460; PCN-bd_Tpept.
DR Pfam; PF00912; Transgly; 1.
DR Pfam; PF00905; Transpeptidase; 1.
DR SUPFAM; SSF53955; SSF53955; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Antibiotic resistance; Carboxypeptidase; Cell membrane;
KW Cell shape; Cell wall; Cell wall biogenesis/degradation;
KW Glycosyltransferase; Hydrolase; Membrane; Multifunctional enzyme;
KW Peptidoglycan synthesis; Protease; Secreted; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..731
FT /note="Penicillin-binding protein 2a"
FT /id="PRO_0000452972"
FT TOPO_DOM 1..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6, ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6, ECO:0000255"
FT TOPO_DOM 78..731
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6, ECO:0000255"
FT REGION 78..300
FT /note="Transglycosylase"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6"
FT REGION 78..156
FT /note="Hydrophobic; associated with cytoplasmic membrane.
FT Required for transglycosylase activity, but not for lipid
FT II binding"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6"
FT REGION 301..731
FT /note="Transpeptidase"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6"
FT REGION 674..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 131
FT /note="Proton donor; for transglycosylase activity"
FT /evidence="ECO:0000250|UniProtKB:Q8DNB6"
FT ACT_SITE 410
FT /note="Acyl-ester intermediate; for transpeptidase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P02919"
SQ SEQUENCE 731 AA; 80799 MW; 159DA81430EEEFDF CRC64;
MKLDKLFEKF LSLFKKETSE LEDSDSTILR RSRSDRKKLA QVGPIRKFWR RYHLTKIILI
LGLSAGLLVG IYLFAVAKST NVNDLQNALK TRTLIFDREE KEAGALSGQK GTYVELTDIS
KNLQNAVIAT EDRSFYKNDG INYGRFFLAI VTAGRSGGGS TITQQLAKNA YLSQDQTVER
KAKEFFLALE LSKKYSKEQI LTMYLNNAYF GNGVWGVEDA SKKYFGVSAS EVSLDQAATL
AGMLKGPELY NPLNSVEDST NRRDTVLQNM VAAGYIDKNQ ETEAAEVDMT SQLHDKYEGK
ISDYRYPSYF DAVVNEAVSK YNLTEEEIVN NGYRIYTELD QNYQANMQIV YENTSLFPRA
EDGTFAQSGS VALEPKTGGV RGVVGQVADN DKTGFRNFNY ATQSKRSPGS TIKPLVVYTP
AVEAGWALNK QLDNHTMQYD SYKVDNYAGI KTSREVPMYQ SLAESLNLPA VATVNDLGVD
KAFEAGEKFG LNMEKVDRVL GVALGSGVET NPLQMAQAYA AFANEGLMPE AHFISRIENA
SGQVIASHKN SQKRVIDKSV ADKMTSMMLG TFTNGTGISS SPADYVMAGK TGTTEAVFNP
EYTSDQWVIG YTPDVVISHW LGFPTTDENH YLAGSTSNGA AHVFRNIANT ILPYTPGSTF
TVENAYKQNG IAPANTKRQV QTNDNSQTDD NLSDIRGRAQ SLVDEASRAI SDAKIKEKAQ
TIWDSIVNLF R
