Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
860  structures 6917  species 0  interactions 40581  sequences 114  architectures

Family: Transpeptidase (PF00905)

Summary: Penicillin binding protein transpeptidase domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Penicillin binding proteins". More...

Penicillin binding proteins Edit Wikipedia article

Ribbon representation of the atomic structure of Penicillin Binding Protein 3 from Pseudomonas aeruginosa (PDB 3OC2),[1] image created with PyMol.
Penicillin-binding protein, transpeptidase
OPM superfamily195
OPM protein5hlb
Penicillin-binding protein, dimerisation domain
PBPs normally catalyze the cross-linking of the bacterial cell wall, but they can be permanently inhibited by penicillin and other β-lactam antibiotics. (NAM = N-acetylmuramic acid; NAG = N-acetylglucosamine)

Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered. All β-lactam antibiotics (except for tabtoxinine-β-lactam, which inhibits glutamine synthetase) bind to PBPs, which are essential for bacterial cell wall synthesis. PBPs are members of a subgroup of enzymes called transpeptidases. Specifically, PBPs are DD-transpeptidases.


There are a large number of PBPs, usually several in each organism, and they are found as both membrane-bound and cytoplasmic proteins. For example, Spratt (1977) reports that six different PBPs are routinely detected in all strains of E. coli ranging in molecular weight from 40,000 to 91,000.[2] The different PBPs occur in different numbers per cell and have varied affinities for penicillin. The PBPs are usually broadly classified into high-molecular-weight (HMW) and low-molecular-weight (LMW) categories.[3] Proteins that have evolved from PBPs occur in many higher organisms and include the mammalian LACTB protein.[4]


PBPs are all involved in the final stages of the synthesis of peptidoglycan, which is the major component of bacterial cell walls. Bacterial cell wall synthesis is essential to growth, cell division (thus reproduction) and maintaining the cellular structure in bacteria. Inhibition of PBPs leads to defects in cell wall structure and irregularities in cell shape, for example filamentation, pseudomulticellular forms, lesions leading to spheroplast formation, and eventual cell death and lysis.

PBPs have been shown to catalyze a number of reactions involved in the process of synthesizing cross-linked peptidoglycan from lipid intermediates and mediating the removal of D-alanine from the precursor of peptidoglycan. Purified enzymes have been shown to catalyze the following reactions: D-alanine carboxypeptidase, peptidoglycan transpeptidase, and peptidoglycan endopeptidase. In all bacteria that have been studied, enzymes have been shown to catalyze more than one of the above reactions.[2] The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (involved in formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (involved in cross-linking of the peptide subunits) and the serine at the active site is conserved in all members of the PBP family.[3]


PBPs bind to β-lactam antibiotics because they are similar in chemical structure to the modular pieces that form the peptidoglycan.[5] When they bind to penicillin, the β-lactam amide bond is ruptured to form a covalent bond with the catalytic serine residue at the PBPs active site. This is an irreversible reaction and inactivates the enzyme.

There has been a great deal of research into PBPs because of their role in antibiotics and resistance. Bacterial cell wall synthesis and the role of PBPs in its synthesis is a very good target for drugs of selective toxicity because the metabolic pathways and enzymes are unique to bacteria.[6] Resistance to antibiotics has come about through overproduction of PBPs and formation of PBPs that have low affinity for penicillins (among other mechanisms such as lactamase production). These experiments change the structure of PBP by adding different amino acids into the protein, allowing for new discovery of how the drug interacts with the protein. Research on PBPs has led to the discovery of new semi-synthetic β-lactams, wherein altering the side-chains on the original penicillin molecule has increased the affinity of PBPs for penicillin, and, thus, increased effectiveness in bacteria with developing resistance.

Presence of the protein penicillin binding protein 2A (PBP2A) is responsible for the antibiotic resistance seen in methicillin-resistant Staphylococcus aureus (MRSA).

The β-lactam ring is a structure common to all β-lactam antibiotics.

Other images

See also

PASTA domain


  1. ^ Sainsbury S, Bird L, Rao V, Shepherd SM, Stuart DI, Hunter WN, Owens RJ, Ren J (January 2011). "Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: comparison of native and antibiotic-bound forms". Journal of Molecular Biology. 405 (1): 173–84. doi:10.1016/j.jmb.2010.10.024. PMC 3025346. PMID 20974151.
  2. ^ a b Spratt BG (1977). "Properties of the penicillin-binding proteins of Escherichia coli K12,". Eur J Biochem. 72 (2): 341–52. doi:10.1111/j.1432-1033.1977.tb11258.x. PMID 319999.
  3. ^ a b Basu J, Chattopadhyay R, Kundu M, Chakrabarti P (1992). "Purification and partial characterization of a penicillin-binding protein from Mycobacterium smegmatis". J Bacteriol. 174 (14): 4829–32. PMC 206282. PMID 1624470.
  4. ^ Peitsaro N, Polianskyte Z, Tuimala J, Pörn-Ares I, Liobikas J, Speer O, Lindholm D, Thompson J, Eriksson O (2008). "Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy". BMC Evolutionary Biology. 8: 16. doi:10.1186/1471-2148-8-26. PMC 2266909. PMID 18226203.
  5. ^ Nguyen-Distèche M, Leyh-Bouille M, Ghuysen JM (1982). "Isolation of the membrane-bound 26 000-Mr penicillin-binding protein of Streptomyces strain K15 in the form of a penicillin-sensitive D-alanyl-D-alanine-cleaving transpeptidase". Biochem J. 207 (1): 109–15. doi:10.1042/bj2070109. PMC 1153830. PMID 7181854.
  6. ^ Chambers HF (1999). "Penicillin-binding protein-mediated resistance in pneumococci and staphylococci". J Infect Dis. 179 Suppl 2: S353–9. doi:10.1086/513854. PMID 10081507.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Penicillin binding protein transpeptidase domain Provide feedback

The active site serine (residue 337 in P14677) is conserved in all members of this family.

Literature references

  1. Pares S, Mouz N, Petillot Y, Hakenbeck R, Dideberg O , Nat Struct Biol 1996;3:284-289.: X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme. PUBMED:8605631 EPMC:8605631

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001460

This signature identifies a large group of proteins, which include:

  • Beta-lactamase precursor ( EC , penicillinase)
  • Peptidoglycan synthetase ftsI ( EC , peptidoglycan glycosyltransferase 3)
  • Methicillin resistance mecR1 protein
  • Methicillin resistance blaR1 protein

The large number of penicillin binding proteins, which are represented in this group of sequences, are responsible for the final stages of peptidoglycan biosynthesis for cell wall formation. The proteins synthesise cross-linked peptidoglycan from lipid intermediates, and contain a penicillin-sensitive transpeptidase carboxy-terminal domain. The active site serine (residue 337 in SWISSPROT ) is conserved in all members of this family [ PUBMED:8605631 ].

MecR1 and BlaR1 are metallopeptidases belonging to MEROPS peptidase family M56, clan M-. BlaR1 and MecR1 cleave their cognate transcriptional repressors BlaI and MecI, respectively, activating the synthesis of MecA.

MecR1 is present in Staphylococcus aureus and Staphylococcus sciuri, whereas BlaR1 (also known as BlaR, PenR1, or PenJ) has been found in Bacillus licheniformis, Staphylococcus epidermidis, Staphylococcus haemolyticus, and several S. aureus strains. These proteins are either plasmid-encoded, chromosomal, or transposon-mediated. MecR1/BlaR1 proteins are made up by homologous N-terminal 330-residue transmembrane metallopeptidase domains linked to extracellular 260-residue homologous PBP-like penicillin sensor moieties.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Beta-lactamase (CL0013), which has the following description:

This superfamily contains proteins that have a beta-lactamase fold. This includes beta-lactamases as well as Dala-Dala carboxypeptidases and glutaminases.

The clan contains the following 6 members:

Beta-lactamase Beta-lactamase2 Glutaminase Peptidase_S11 Peptidase_S13 Transpeptidase


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A & Pfam-B_726 (Release 8.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Finn RD
Number in seed: 40
Number in full: 40581
Average length of the domain: 288.00 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 42.50 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.1 22.1
Trusted cut-off 22.1 22.1
Noise cut-off 22.0 22.0
Model length: 306
Family (HMM) version: 24
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Transpeptidase domain has been found. There are 860 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...