Penicillin-binding proteins

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Penicillin binding protein
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Penicillin-binding protein, transpeptidase
Identifiers
SymbolPCN-bd_Tpept
PfamPF00905
InterProIPR001460
OPM superfamily195
OPM protein5hlb
Membranome541
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Penicillin-binding protein, dimerisation domain
Identifiers
SymbolPBP_dimer
PfamPF03717
InterProIPR005311
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDBPDB: 1k25​ PDB: 1mwr​ PDB: 1mws​ PDB: 1mwt​ PDB: 1mwu​ PDB: 1pmd​ PDB: 1pyy​ PDB: 1qme​ PDB: 1qmf​ PDB: 1rp5​
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)[2]

Penicillin-binding proteins (PBPs) are a group of

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
.

Diversity

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.[3] 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.[4] Proteins that have evolved from PBPs occur in many higher organisms and include the mammalian LACTB protein.[5]

Function

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.[2] 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.[6]

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-

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.[4]

Some low-molecular-weight PBPs associate with the MreB cytoskeleton and follow its rotation around the cell, inserting petipdoglycan in an oriented manner during cell growth.[7] In contrast, high-molecular-weight PBPs are independent from MreB and maintain cell wall integrity by detecting and repairing defects in the peptidoglycan.[8]

Antibiotics

PBPs bind to

β-lactam antibiotics because they are similar in chemical structure to the modular pieces that form the peptidoglycan.[9]
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.

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).[11]

The β-lactam ring is a structure common to all β-lactam antibiotics.[12]

Other images

  • Penicillin core.[13]
    Penicillin core.[13]
  • Filamentation (top right of electron micrograph) occurs in some bacteria when PBP3 is inhibited.[6]
    Filamentation (top right of electron micrograph) occurs in some bacteria when PBP3 is inhibited.[6]

See also

PASTA domain

References

  1. PMID 20974151
    .
  2. ^
    S2CID 210814189
    .
  3. ^
    PMID 319999
    .
  4. ^
    PMID 1624470
    .
  5. PMID 18226203
    .
  6. ^
    S2CID 2065821. Archived
    from the original on 2017-10-07. Retrieved 2020-05-01.
  7. PMID 31086310
    .
  8. PMID 31904338
    .
  9. PMID 7181854
    .
  10. PMID 10081507
    .
  11. PMID 2708325
    .
  12. PMID 31424895. Archived
    from the original on 2020-12-15. Retrieved 2020-05-01.
  13. ISBN 9781437703108. Archived
    from the original on 2020-07-05. Retrieved 2020-05-01.
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