title: Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria.
abstract: The solution structure of three small serine proteinase inhibitors, two natural and one engineered protein, SGCI (Schistocerca gregaria chymotrypsin inhibitor), SGCI[L30R, K31M] and SGTI (Schistocerca gregaria trypsin inhibitor), were determined by homonuclear NMR-spectroscopy. The molecules exhibit different specificities towards target proteinases, where SGCI is a good chymotrypsin inhibitor, its mutant is a potent trypsin inhibitor, and SGTI inhibits both proteinases weakly. Interestingly, SGTI is a much better inhibitor of insect proteinases than of the mammalian ones used in common assays. All three molecules have a similar fold composed from three antiparallel beta-pleated sheets with three disulfide bridges. The proteinase binding loop has a somewhat distinct geometry in all three peptides. Moreover, the stabilization of the structure is different in SGCI and SGTI. Proton-deuterium exchange experiments are indicative of a highly rigid core in SGTI but not in SGCI. We suggest that the observed structural properties play a significant role in the specificity of these inhibitors.
authors.affiliation: Department of Organic Chemistry, Eötvös L University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gáspári
authors.forename: András
authors.initials: A
authors.lastname: Patthy
authors.forename: László
authors.initials: L
authors.lastname: Gráf
authors.forename: András
authors.initials: A
authors.lastname: Perczel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D006110:Grasshoppers / Q000737:chemistry*; D019476:Insect Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*; D010455:Peptides
chemical_list: D019476:Insect Proteins; D015842:Serine Proteinase Inhibitors; C113210:LOC126284306 protein, Schistocerca gregaria; D010455:Peptides