Peptidoglycan endopeptidase RipA (RipA)

Peptidoglycan endopeptidase RipA (Rv3396c) is a vital secreted enzyme produced by Mycobacterium tuberculosis that facilitates the remodeling of the bacterial cell wall. It functions primarily as an L-alanine-D-glutamate peptidase, belonging to the NlpC/P60 family, and is responsible for cleaving peptide linkages within the peptidoglycan layer to allow for daughter cell separation during division (Chao et al., 2013, Nature Communications; Ruggiero et al., 2010, Journal of Molecular Biology). RipA is particularly significant for its role in the resuscitation of the pathogen from a dormant or non-replicating state, often working in complex with resuscitation-promoting factors like RpfB (Böth et al., 2011, Journal of Biological Chemistry). Because RipA is essential for M. tuberculosis growth and is localized to the cell wall and extracellular environment, it is considered a high-priority target for new antitubercular drug development. Inhibiting this enzyme disrupts the bacterial life cycle and can sensitize the pathogen to other antibiotics that target cell wall synthesis (UniProt P9WKI1). While no clinical drugs currently target RipA, it remains a focus of intensive research for small-molecule inhibitor discovery to combat multi-drug resistant tuberculosis (NIH/NCBI Gene ID: 887050).

Other names

Rv3396cL-alanine-D-glutamate peptidaseD,L-endopeptidase RipAResuscitation-promoting factor-interacting protein ASecreted L-alanine-D-glutamate peptidase

Inhibition of peptidoglycan cross-link cleavage, leading to impaired cell division and cell wall instability.