the energetics of conformational interconversions plasminogen

纤溶酶原构象相互转化的能量学

• 批准号: 9988-2006
• 负责人: Kornblatt, Jack
• 金额: $ 3.22万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=337061
• 关键词: energetics; conformational; interconversions; plasminogen

We study the blood protein, plasminogen.  It is the body's first line of defense against unwanted, internal blood clots.  It is also involved in tissue remodeling such as occurs during lactation and tumour metastasis.  Plasminogen binds to a clot or cell, opens and can then be activated to plasmin, the enzymatic form.  On binding, the plasminogen undergoes a large conformational change; it is part of the activation process.  Our long term goal is to be able to activate plasminogen at will when it is desirable, and inhibit its activation when it is undesirable.  In order to do that we need a firm grasp of the factors that dictate which conformations are present, when they are present and what promotes or inhibits their interconversion.

我们研究血液蛋白纤溶酶原，它是人体对抗不需要的内部血栓的第一道防线，它还参与组织重塑，例如在哺乳期间和肿瘤转移期间发生的纤溶酶原与凝块或细胞结合并打开。然后被激活为纤溶酶（酶形式）。​结合后，纤溶酶原会发生较大的构象变化，这是激活的一部分；我们的长期目标是能够在需要时随意激活纤溶酶原，并在不需要时抑制其激活。为了做到这一点，我们需要牢牢掌握决定哪些构象何时存在的因素。它们的存在以及促进或抑制它们相互转化的因素。