NMR STUDIES OF THE COMPLEX OF SCHISTOCERCA GREGARIA CHYMOTRYPSIN INHIBITOR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在我们提出的研究中，我们的目的是通过设计、合成和构效关系研究凝乳酶抑制剂模型多肽来帮助理解天然蛋白水解酶抑制的原理。我们的基本假设是，通过结合环和结构相关残基的组合构建的模型分子可以有效地研究酶抑制的结构性质，并为其定义一个适当的“支架”。被选为模型的分子是SGCI(Schistocerca Gregaria Chymotrypsin Inhibitor)，一种高效的35个残基的Chymotrypsin抑制剂(Ki=6.20*10-12)。我们之前已经制备了三个模型多肽，它们揭示了多肽支架在维持蛋白水解酶结合环的正确构象和流动性方面的关键作用。将对SGCI-糜蛋白酶配体-蛋白质复合体进行研究，以揭示相互作用表面的大小和性质。我们相信，我们的方法在更好地理解典型的丝氨酸蛋白酶抑制机制和其他生物学上有趣的系统方面都被证明是有用的。

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.