This family includes insulin-cleaving membrane protease (imelysin, ICMP)-like protein (IPPA from Psychrobacter arcticus), the Pseudomonas aeruginosa PA4372 and Vibrio cholera VC1266 Fur-regulated imelysin-like protein. They share the overall fold and a similar functional site as the insulin-cleaving membrane protease (ICMP). However, IPPA adopts a structure distinctive from the known HxxE metallopeptidases or iron-binding proteins, suggesting this protein may not be a peptidase; the histidine in the GxHxxE motif region is no longer conserved (GxxxxE), indicating a possible loss of enzymatic function or a change in substrate preference (compared to imelysin and IrpA families). A putative functional site for this non-peptidase homolog is located at the domain interface. The tertiary structure shows a fold consisting of two domains, each of which consists of a bundle of four helices that are similar to each other, implying an ancient gene duplication and fusion event.
Jiyao W et al.(2023). "The conserved domain database in 2023.",