?
Peptidase M4 family containing mostly uncharacterized proteins This family of uncharacterized bacterial proteins are homologs of the M4 peptidase family that is also known as the thermolysin-like peptidase (TLP) family. Typically, the M4 peptidases consist of a presequence (signal sequence), a propeptide sequence and a peptidase unit. The presequence is cleaved off during export while the propeptide has inhibitory and chaperone functions and facilitates folding. The propeptide remains attached until the peptidase is secreted and can be safely activated. All peptidases in this family bind a single catalytic zinc ion which is tetrahedrally co-ordinated by three amino acid ligands and a water molecule that forms the nucleophile on activation during catalysis. TLPs are secreted eubacterial endopeptidases from Gram-positive or Gram-negative sources that degrade extracellular proteins and peptides for bacterial nutrition. They contain the HEXXH motif as part of their active site and belong to the Gluzincins family and are selectively inhibited by Steptomyces metalloproteinase inhibitor (SMPI) as well as by phosphoramidon from Streptomyces tanashiensis. A large number of these enzymes are implicated as key factors in the pathogenesis of various diseases, including gastritis, peptic ulcer, gastric carcinoma, cholera and several types of bacterial infections, and are therefore important drug targets. Some enzymes of the family can function at extremes of temperatures, while some function in organic solvents, thus rendering them novel targets for biotechnological applications. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",