Expression is induced in macrophages and infected mice (PubMed:16672626). Highly up-regulated during the early stages of invasion of the human blood-brain barrier (PubMed:16586367). Contains an aspartic proteinase-like domain in the C-terminal region. However, the enzyme is inactive. A comparison of the structure with pepsins showed significant differences in the critical substrate binding residues and in the flap tyrosine conformation that could contribute to the lack of proteolytic activity of PE_PGRS16. Expression of this gene in M.smegmatis leads to increased levels of NO and IL-12 and poor survival of recombinant strains in macrophages. Contains a tightly bound zinc ion. The presence of this ion is unexpected, and two His residues from the hexahistidine tag on the expression vector contribute to the zinc binding site. Belongs to the mycobacterial PE family. PGRS subfamily.