NMR STUDIES OF THE COMPLEX OF SCHISTOCERCA GREGARIA CHYMOTRYPSIN INHIBITOR

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在我们提出的研究中，我们的目标是通过设计，合成和结构-活性研究胰凝乳蛋白酶抑制剂模型肽的天然蛋白酶抑制的原理的理解。我们的基本假设是，酶抑制的结构特性可以有效地研究与模型分子的结合环和结构相关的残基定义一个适当的'支架'为it. The分子被选择来建模是SGCI（Schistocerca gregaria chymotrypsin inhibitor），一个高效的，35-残基chymotrypsin抑制剂（Ki=6.20*10-12）的组合。我们先前已经制备了三种模型肽，揭示了肽支架在维持蛋白酶结合环的正确构象和流动性方面的关键作用。将研究SGCI-糜蛋白酶配体-蛋白质复合物以揭示相互作用表面的大小和性质。我们相信，我们的方法证明是有用的，在更好地理解经典的丝氨酸蛋白酶抑制和其他生物有趣的系统的机制。

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.