NMR STUDIES OF THE COMPLEX OF SCHISTOCERCA GREGARIA CHYMOTRYPSIN INHIBITOR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In our proposed research we aim to contribute to the understanding of the principles of natural protease inhibition by design, synthesis and structure-activity investigation of chymotrypsin inhibitor model peptides. Our basic assumption is that the structural properties of enzyme inhibition can be effectively studied with model molecules constructed by the combination of the binding loop and structurally relevant residues defining a proper 'scaffold' for it. The molecule chosen to be modeled is SGCI (Schistocerca gregaria chymotrypsin inhibitor), a highly potent, 35-residue chymotrypsin inhibitor (Ki=6.20*10-12). We have previously prepared three model peptides which revealed the crucial role of the peptide scaffold in maintaining the proper conformation and mobility of the protease binding loop. The SGCI-chymotripsin ligand-protein complex will be studied to reveal the size and nature of the interacting surfaces. We believe our approach proves useful both in better understanding of the mechanism of canonical serine protease inhibition and other biologically interesting systems.