ANTICOAGULANT PROTEIN STRUCTURE AND FUNCTION

抗凝蛋白的结构和功能

• 批准号: 7598562
• 负责人: TIMOTHY A. MATHER
• 金额: $ 3.07万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598562
• 关键词: Active Sites; Antibodies; Anticoagulants; Aprotinin; Binding; Binding Sites; Calcium; Calcium Binding; Class; Coenzymes; Companions; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Image; Institution; Metal Binding Site; Metals; Pathway interactions; Reporting; Research; Research Personnel; Resources; Source; Spottings; Structure; Study models; Testing; Thrombin; Thrombomodulin; Twin Multiple Birth; United States National Institutes of Health; antigen binding; inhibitor/antagonist; protein structure function

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 衍射质量和实验计划：我们每种晶体的测试图像表明镶嵌性低，没有双胞胎的迹象。我们计算100％完整性的以下扫描：晶体1：94摄氏度2：116摄氏度晶体3：122度。 重要性：晶体1具有独特的钙依赖性抗体，抗体本身内具有金属结合位点。然而，建模研究表明，与亨德里克森（Hendrickson）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作用非常独特（Zhou等人PNAS 102：14575（2005））。该结构应提供有关该单克隆人的金属和抗原结合能力的信息。 Crystal 2是对具有未抑制活性位点的这种重要酶伴侣络合物的首次看。因此，我们希望更多地了解血小板蛋白对凝血酶活性部位的变构作用，因为它将凝血酶从凝血蛋白转换为抗凝剂途径。 Crystal 3将Kazal类抑制剂牛胰腺胰蛋白酶抑制剂（BPTI）添加到Ctystal 2复合物中。这很重要，因为BPTI不单独与凝血酶结合，并且仅抑制血栓 - 肉毒杆菌蛋白复合物。这种结构应预测有关血小板蛋白的变构作用的大量信息，并且是Crystal 2的自然伴侣结构。