Target intelligence / Profile preview

Peptidoglycan hydrolase PcsB (PcsB) (PcsB)

Target
PcsB
Molecular classification
Enzyme, Peptidoglycan hydrolase, Cell cycle protein, Hydrolase
01

Overview

Peptidoglycan hydrolase PcsB (PcsB) is a highly conserved enzyme essential for cell wall remodeling and daughter cell separation in Streptococcus pneumoniae and other streptococci. It contains a catalytic cysteine- and histidine-dependent aminohydrolase/peptidase (CHAP) domain and a regulatory coiled-coil domain that mediates auto-inhibition. PcsB is regulated by the WalRK (VicRK) two-component system and is activated through its interaction with the FtsEX cell division complex at the septum. Because of its essential role in bacterial viability and its high conservation across serotypes, PcsB is a prominent target for the development of novel antibiotics and vaccines. Inhibition or depletion of PcsB leads to severe defects in cell division, characterized by the formation of large cell clusters and increased sensitivity to osmotic stress and existing antibiotics. A trivalent vaccine candidate (IC47) containing recombinant PcsB has been evaluated in Phase 1 clinical trials and shown to be safe and immunogenic in humans.

Other names
Protein required for cell separation BPneumococcal cell wall separation proteinusp45SP_2216p50Sep1IDG60
02

Mechanism of action

Induction of protective antibodies and opsonophagocytic killing; potential inhibition of peptidoglycan hydrolysis and cell division

03

Biological functions

Cell divisionPeptidoglycan remodelingSeptum separationMaintenance of cell morphologyResponse to environmental stress
04

Disease associations

InfectionPneumoniaMeningitisSepsisNeonatal infection
05

Safety considerations

Essentiality variation across strainsCapsule interference with antibody accessibilityAuto-inhibition of catalytic activity in vitro
06

Interacting drugs

IC47 (Pneumococcal vaccine candidate)

3 more in the full profile.

07

Biomarkers

PcsB-specific IgG levelsPcsB expression levels

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