Crystal structure of greglin, a novel non-classical Kazal inhibitor, in complex with subtilisin.

摘要: Greglin is an 83-residue serine protease inhibitor purified from the ovaries of locust Schistocerca gregaria. a strong subtilisin and human neutrophil elastase, acting at sub-nanomolar nanomolar concentrations, respectively; it also inhibits cathepsin G, α-chymotrypsin porcine pancreatic but to lesser extent. In present study, we show that greglin resists denaturation high temperature (95 °C) after exposure acetonitrile acidic or basic pH. composed two domains consisting residues 1–20 21–83. Mass spectrometry indicates N-terminal domain (1–20) post-translationally modified by phosphorylations three sites probably contains glycosylation site. The crystal structure region comprising 21–78 in complex with was determined 1.75 A resolution. represents novel member non-classical Kazal inhibitors, as has unique additional C-terminal (70–83) connected core molecule via supplementary disulfide bond. stability compared ovomucoid inhibitor. thermostability inhibitory specificity are discussed light its structure. particular, propose responsible for non-favourable interactions autolysis loop (140-loop) proteases chymotrypsin family, thus governs specificity. Database The atomic coordinates factors greglin–subtilisin have been deposited RCSB Protein Data Bank under accession number 4GI3. Structured digital abstract Greglin Subtilisin Carlsberg bind X-ray crystallography (View interaction)