Search

The M4 family proteins are common eubacterial metallopeptidases that are involved in a range of functions from nutrient production to pathogenicity. Typically, they consist of a propeptide with inhibitory and chaperone functions and a peptidase unit. The propeptide is cleaved but remains attached until the peptidase is secreted and can be safely activated. Here, we describe a domain in the propeptide that is likely to contain the inhibitory activity, but not the chaperone activity, it is also in many non-peptidase proteins, including Bacillus subtilis YpeB protein--a regulator of SleB spore cortex lytic enzyme--and a large number of eubacterial and archaeal cell-wall-associated and secreted proteins. We propose that it acts as a regulator of peptidase activity in the local environment and also protects the cell from lysis.

Cleavage of peptidoglycan plays an important role in bacterial cell division, cell growth and cell lysis. Here, we reveal that several known peptidoglycan amidases fall into a family, which includes many proteins of previously unknown function. The family includes two different peptidoglycan cleavage activities: L-muramoyl-L-alanine amidase and D-alanyl-glycyl endopeptidase activity. The family includes the amidase portion of the bifunctional glutathionylspermidine synthase/amidase enzyme from bacteria and pathogenic trypanosomes. The glutathionylspermidine synthase is thought to be a key component of the alternative pathway in trypanosomes for protection from oxygen-radical damage and has been proposed as a potential drug target. The CHAP (cysteine, histidine-dependent amidohydrolases/peptidases) domain is often found in association with other domains that cleave peptidoglycan. The large number of multifunctional hydrolases suggests that they might act in a cooperative manner to cleave specialized substrates.