Pyrroloquinoline quinone (PQQ), a prominent redox cofactor in a variety of prokaryotes, is produced from a ribosomally synthesized and post-translationally modified peptide PqqA via a pathway comprised of four conserved proteins PqqB-PqqE. These four proteins are now fairly well characterized and span Radical SAM activity (PqqE), aided by a peptide chaperone (PqqD), a dual hydroxylase (PqqB), and an eight electron, eight proton oxidase (PqqC). A full description of this pathway has been hampered by a lack of information regarding a protease/peptidase required for the excision of an early, cross-linked di-amino acid precursor to PQQ.
UC Berkeley researchers have isolated and characterized a two component, heterodimer protein that is able to rapidly catalyze cleavage of PqqA into smaller peptides. The UC researchers have developed: novel proteases that can cut peptide bonds both N- and C- terminal to the amino acid serine; compositions comprising such proteases; and methods of use, including to assay the extent, position, and time course of protein phosphorylation at serine side chains.