ANTICOAGULANT PROTEIN STRUCTURE AND FUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 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。 衍射质量和实验计划： 我们每个晶体的测试图像都显示出低镶嵌性的脆点，没有孪生迹象。我们计算以下扫描的100%完整性： 晶体1：94度 晶体2：116度 晶体3：122度 重要性： 晶体1是一种独特的钙依赖性抗体，在抗体本身内具有金属结合位点。然而，建模研究表明，与Hendrickson小组报道的钙依赖性抗体的唯一其他结构相比，我们的钙结合位点和金属结合的构象效应是非常独特的（Zhou等人，PNAS 102：14575（2005））。该结构应提供关于该单克隆抗体的金属和抗原结合能力的信息。 晶体2是第一次看到这个重要的酶辅因子复合物与一个不受抑制的活性位点。因此，我们希望了解更多关于变构效应，血栓调节蛋白对凝血酶的活性位点，因为它开关凝血酶从其促凝血活性的抗凝途径。 晶体3将kazal类抑制剂牛胰蛋白酶抑制剂（BPTI）添加到晶体2复合物中。这是重要的，因为BPTI不单独与凝血酶结合，而仅抑制血栓-血栓调节蛋白复合物。该结构应提供关于血栓调节蛋白的变构效应的丰富信息，并且是晶体2的天然伴侣结构。

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. Diffraction quality and experimental plan: Test images of each of our crystals indicate crisp spots with low mosaicity and no indication of twinning. We calculate the following sweeps for 100 % completeness: crystal 1: 94 deg crystal 2: 116 deg crystal 3: 122 deg. Importance: Crystal 1 is of a unique calcium dependent antibody with metal binding sites within the antibody itself. However, modelling studies indicate that our calcium binding sites and the conformational effects of metal binding are quite unique compared to the only other structure of a calcium dependent antibody reported by Hendrickson`s group (Zhou et al. PNAS 102:14575 (2005)). This structure should provide information on both the metal and antigen binding ability of this monoclonal. Crystal 2 is the first look at this important enzyme-cofactor complex with an uninhibited active site. As such we expect to understand more about the allosteric effect that thrombomodulin has on thrombin`s active site as it switches thrombin from its procoagulant activity to the anticoagulant pathway. Crystal 3 adds the kazal class inhibitor Bovine Pancreatic Trypsin Inhibitor (BPTI) to the ctystal 2 complex. This is significant because BPTI does not bind to thrombin alone and only inhibits the thrombon-thrombomodulin complex. This structure should prorvide a wealth of information about the allosteric effect of thrombomodulin and is a natural companion structure to crystal 2.