PBP2A_STRR6
ID PBP2A_STRR6 Reviewed; 731 AA.
AC Q8DNB6; O70039;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Penicillin-binding protein 2a {ECO:0000303|PubMed:10217767, ECO:0000303|PubMed:12867450, ECO:0000303|PubMed:22487093, ECO:0000303|PubMed:9537382};
DE Short=PBP2a {ECO:0000303|PubMed:10217767, ECO:0000303|PubMed:12867450, ECO:0000303|PubMed:22487093, ECO:0000303|PubMed:9537382};
DE AltName: Full=Cell wall synthase PBP2a {ECO:0000305};
DE Includes:
DE RecName: Full=Penicillin-insensitive transglycosylase {ECO:0000305};
DE EC=2.4.1.129 {ECO:0000269|PubMed:12867450, ECO:0000269|PubMed:22487093};
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:0000269|PubMed:10217767, ECO:0000269|PubMed:22487093};
DE AltName: Full=DD-transpeptidase {ECO:0000305};
GN Name=pbp2a {ECO:0000312|EMBL:AAL00626.1, ECO:0000312|EMBL:CAA05303.1};
GN OrderedLocusNames=spr1823 {ECO:0000312|EMBL:AAL00626.1};
OS Streptococcus pneumoniae (strain ATCC BAA-255 / R6).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=171101 {ECO:0000312|EMBL:AAL00626.1};
RN [1] {ECO:0000312|EMBL:CAA05303.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC BAA-255 / R6 {ECO:0000303|PubMed:9537382,
RC ECO:0000312|EMBL:CAA05303.1};
RX PubMed=9537382; DOI=10.1128/jb.180.7.1831-1840.1998;
RA Hakenbeck R., Konig A., Kern I., van der Linden M., Keck W.,
RA Billot-Klein D., Legrand R., Schoot B., Gutmann L.;
RT "Acquisition of five high-Mr penicillin-binding protein variants during
RT transfer of high-level beta-lactam resistance from Streptococcus mitis to
RT Streptococcus pneumoniae.";
RL J. Bacteriol. 180:1831-1840(1998).
RN [2] {ECO:0000312|EMBL:AAL00626.1, ECO:0000312|Proteomes:UP000000586}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-255 / R6 {ECO:0000312|Proteomes:UP000000586};
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 [3]
RP PROTEIN SEQUENCE OF 78-81; 156-161; 264-267 AND 301-304, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, TOPOLOGY, AND REGIONS.
RC STRAIN=ATCC BAA-255 / R6 {ECO:0000303|PubMed:10217767};
RX PubMed=10217767; DOI=10.1128/jb.181.9.2773-2781.1999;
RA di Guilmi A.M., Mouz N., Martin L., Hoskins J., Jaskunas S.R., Dideberg O.,
RA Vernet T.;
RT "Glycosyltransferase domain of penicillin-binding protein 2a from
RT Streptococcus pneumoniae is membrane associated.";
RL J. Bacteriol. 181:2773-2781(1999).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, DOMAIN, BIOTECHNOLOGY, TOPOLOGY, AND
RP REGIONS.
RC STRAIN=ATCC BAA-255 / R6 {ECO:0000303|PubMed:12867450};
RX PubMed=12867450; DOI=10.1128/jb.185.15.4418-4423.2003;
RA Di Guilmi A.M., Dessen A., Dideberg O., Vernet T.;
RT "The glycosyltransferase domain of penicillin-binding protein 2a from
RT Streptococcus pneumoniae catalyzes the polymerization of murein glycan
RT chains.";
RL J. Bacteriol. 185:4418-4423(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, MASS SPECTROMETRY,
RP TOPOLOGY, ACTIVE SITE, AND MUTAGENESIS OF GLU-131.
RC STRAIN=ATCC BAA-255 / R6 {ECO:0000303|PubMed:22487093};
RX PubMed=22487093; DOI=10.1111/j.1742-4658.2012.08592.x;
RA Helassa N., Vollmer W., Breukink E., Vernet T., Zapun A.;
RT "The membrane anchor of penicillin-binding protein PBP2a from Streptococcus
RT pneumoniae influences peptidoglycan chain length.";
RL FEBS J. 279:2071-2081(2012).
RN [6]
RP SUBUNIT.
RC STRAIN=R6 / R704;
RX PubMed=28710862; DOI=10.1111/mmi.13748;
RA Stamsaas G.A., Straume D., Ruud Winther A., Kjos M., Frantzen C.A.,
RA Haavarstein L.S.;
RT "Identification of EloR (Spr1851) as a regulator of cell elongation in
RT Streptococcus pneumoniae.";
RL Mol. Microbiol. 105:954-967(2017).
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
CC (PubMed:12867450, PubMed:22487093). Hydrolyzes S2d (N-benzoyl-D-
CC alanylmercaptoacetic acid) molecule, a synthetic thiolester analog of
CC cell wall stem peptide (PubMed:10217767, PubMed:22487093). Active
CC against bocillin, a fluorescent penicillin. No transpeptidase activity
CC with non-fluorescent lysine-containing lipid II as substrate
CC (PubMed:22487093). {ECO:0000250|UniProtKB:P02918,
CC ECO:0000269|PubMed:10217767, ECO:0000269|PubMed:12867450,
CC ECO:0000269|PubMed:22487093}.
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:0000269|PubMed:10217767, ECO:0000269|PubMed:22487093};
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:0000269|PubMed:12867450, ECO:0000269|PubMed:22487093};
CC -!- ACTIVITY REGULATION: Optimal transglycosylase/glycosyltransferase (GT)
CC activity in the presence of 30-40% dimethylsulfoxide and 0.002% Triton
CC X-100. High GT activity in the presence of CHAPS, Triton X-100 and n-
CC dodecyl-beta-D-maltopyranoside (DDM) detergents, and to a lesser extent
CC in the presence of Cymal-5 (PubMed:22487093). GT activity is inhibited
CC by moenomycin (PubMed:12867450, PubMed:22487093). 50% inhibition of the
CC GT activity with 2.8 uM moenomycin. No effect on GT activity detected
CC with 2.8 uM vancomycin, but complete inhibition with 28 uM vancomycin
CC (PubMed:12867450). No GT activity in the presence of n-octyl-beta-D-
CC glucopyranoside, Cymal-3 and Cymal-4 detergents (PubMed:22487093).
CC {ECO:0000269|PubMed:12867450, ECO:0000269|PubMed:22487093}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40.6 uM for dansylated lipid II {ECO:0000269|PubMed:12867450};
CC Vmax=0.38 nmol/min/mg enzyme with lysine-dansylated lipid II as
CC substrate (at pH 7.5 and 30 degrees Celsius in the presence of 25%
CC dimethylsulfoxide and 0.04 Triton X-100)
CC {ECO:0000269|PubMed:22487093};
CC Vmax=403 nmol/min/mg enzyme for the hydrolysis of S2d (N-benzoyl-D-
CC alanylmercaptoacetic acid) (at pH 7.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:22487093};
CC Note=kcat is greater than 0.0005 sec(-1) with dansylated lipid II as
CC substrate (PubMed:22487093). kcat/KM is 0.001 M(-1)sec(-1) with
CC dansylated lipid II as substrate (PubMed:12867450).
CC {ECO:0000269|PubMed:12867450, ECO:0000269|PubMed:22487093};
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 (PubMed:22487093). Interacts with MacP; interaction is required for the
CC function of this protein (By similarity). Interacts with MreC in the
CC elongasome (PubMed:28710862). {ECO:0000250|UniProtKB:A0A0H2ZMF9,
CC ECO:0000269|PubMed:22487093, ECO:0000269|PubMed:28710862}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10217767,
CC ECO:0000269|PubMed:12867450, ECO:0000269|PubMed:22487093}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:10217767,
CC ECO:0000269|PubMed:12867450, ECO:0000269|PubMed:22487093}. Secreted,
CC cell wall {ECO:0000305}. Note=Localizes to sites of new peptidoglycan
CC (PG) synthesis at midcell independently of MacP.
CC {ECO:0000250|UniProtKB:A0A0H2ZMF9}.
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)
CC (PubMed:10217767, PubMed:12867450, PubMed:22487093). Transmembrane
CC signal-anchor is required for the synthesis of longer, 20-30
CC disaccharide units containing, glycan chains (PubMed:22487093).
CC {ECO:0000269|PubMed:10217767, ECO:0000269|PubMed:12867450,
CC ECO:0000269|PubMed:22487093}.
CC -!- MASS SPECTROMETRY: Mass=80797; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:22487093};
CC -!- BIOTECHNOLOGY: Transglycosylase/glycosyltransferase (GT) domain of this
CC protein may be an alternative target for the development of new
CC inhibitors of S.pneumoniae as the beta-lactam antibiotics targeted
CC against the transpeptidase domain of this protein have increasing
CC resistance. {ECO:0000305|PubMed:12867450}.
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; AJ002292; CAA05303.1; -; Genomic_DNA.
DR EMBL; AE007317; AAL00626.1; -; Genomic_DNA.
DR PIR; E98099; E98099.
DR RefSeq; NP_359415.1; NC_003098.1.
DR RefSeq; WP_000762624.1; NC_003098.1.
DR AlphaFoldDB; Q8DNB6; -.
DR SMR; Q8DNB6; -.
DR MINT; Q8DNB6; -.
DR STRING; 171101.spr1823; -.
DR DrugBank; DB01163; Amdinocillin.
DR DrugBank; DB00415; Ampicillin.
DR DrugBank; DB08795; Azidocillin.
DR DrugBank; DB00456; Cefalotin.
DR DrugBank; DB00493; Cefotaxime.
DR DrugBank; DB01331; Cefoxitin.
DR DrugBank; DB00567; Cephalexin.
DR DrugBank; DB03313; Cephalosporin C.
DR DrugBank; DB00485; Dicloxacillin.
DR DrugBank; DB00739; Hetacillin.
DR DrugBank; DB01603; Meticillin.
DR DrugBank; DB00607; Nafcillin.
DR DrugBank; DB00713; Oxacillin.
DR DrugBank; DB00319; Piperacillin.
DR CAZy; GT51; Glycosyltransferase Family 51.
DR EnsemblBacteria; AAL00626; AAL00626; spr1823.
DR GeneID; 60233563; -.
DR KEGG; spr:spr1823; -.
DR PATRIC; fig|171101.6.peg.1967; -.
DR eggNOG; COG0744; Bacteria.
DR HOGENOM; CLU_006354_2_2_9; -.
DR OMA; AVQMPYI; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000000586; 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; IBA:GO_Central.
DR GO; GO:0008955; F:peptidoglycan glycosyltransferase activity; IBA:GO_Central.
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; IBA:GO_Central.
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; IBA:GO_Central.
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 Direct protein sequencing; Glycosyltransferase; Hydrolase; Membrane;
KW Multifunctional enzyme; Peptidoglycan synthesis; Protease;
KW Reference proteome; Secreted; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..731
FT /note="Penicillin-binding protein 2a"
FT /id="PRO_0000452973"
FT TOPO_DOM 1..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:10217767,
FT ECO:0000305|PubMed:12867450, ECO:0000305|PubMed:22487093"
FT TRANSMEM 57..77
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:10217767,
FT ECO:0000305|PubMed:12867450, ECO:0000305|PubMed:22487093"
FT TOPO_DOM 78..731
FT /note="Extracellular"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:10217767,
FT ECO:0000305|PubMed:12867450, ECO:0000305|PubMed:22487093"
FT REGION 78..300
FT /note="Transglycosylase"
FT /evidence="ECO:0000305|PubMed:10217767,
FT ECO:0000305|PubMed:12867450"
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:0000269|PubMed:10217767,
FT ECO:0000269|PubMed:12867450"
FT REGION 301..731
FT /note="Transpeptidase"
FT /evidence="ECO:0000305|PubMed:10217767,
FT ECO:0000305|PubMed:12867450"
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:0000269|PubMed:22487093"
FT ACT_SITE 410
FT /note="Acyl-ester intermediate; for transpeptidase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P02919"
FT MUTAGEN 131
FT /note="E->Q: Loss of transglycosylase activity with
FT dansylated lipid II as substrate."
FT /evidence="ECO:0000269|PubMed:22487093"
FT CONFLICT 704
FT /note="D -> N (in Ref. 1; CAA05303)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="R -> H (in Ref. 1; CAA05303)"
FT /evidence="ECO:0000305"
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
