Ribbon rendering of the structure of AC-IV in Yersina pestis as determined at NIST. The enzyme is a dimer (two identical subunits around a vertical axis), and each of the...
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美国标准技术研究院（NIST）已经破解了来源于鼠疫杆菌的一种关键酶的结构，并且发现它具有一种非常特别的构型。这些结果揭示出了这种细菌毒性机制和相关的基础细胞信号过程。
NIST研究组确定出了IV腺嘌呤环化酶（AC-IV）的三维结构，这种酶存在于曾引发人类瘟疫的鼠疫杆菌（Yersinia pestis）中。通过提纯和结晶这种蛋白质，然后用X射线晶体衍射技术，研究人员最终破译了这种关键酶的构型。这种酶能够合成环形AMP(cAMP)——一种能引发多种细胞过程的重要信号分子。目前已经知道了六种类型的AC，并且起到多种功能。
在决定一个蛋白质的生物功能时，蛋白质的形状起到决定性作用，但是由于这种酶分子很大，因此形状的确定很困难。NIST的实验表明AC-IV的形状与其他已知结构的AC（AC-II和AC-III）完全不同。AC-IV折叠成一种罕见的水桶状。此前，这种形状只在另外三种不相关的蛋白质发现过。
虽然AC-IV在鼠疫中的作用机制还不是很清楚，但是研究人员推测它可能干扰被感染寄主的细胞过程。这种酶的基础分子信息和它的不同构型信息可能是人类开发应对这种瘟疫和其他病原物的关键。
英文原文：
Structure of key enzyme in plague bacterium found
Researchers at the National Institute of Standards and Technology (NIST) have solved the structure of a key enzyme from the bacterium responsible for plague, finding that it has a highly unusual configuration. The results may shed light both on how the bacterium kills and on fundamental cell signaling processes.
The NIST team determined the three-dimensional shape of class IV adenylyl cyclase (AC), an enzyme found in plague bacteria -- Yersinia pestis -- by purifying and crystallizing the protein and using X-ray crystallography at the Center for Advanced Research in Biotechnology to resolve its configuration. Adenylyl cyclase is a fundamental enzyme found in one form or another in organisms ranging from bacteria to mammals. It synthesizes cyclic AMP (cAMP*), an important signaling molecule that in turn triggers a variety of cellular processes. Six distinct classes of AC are known, playing a wide variety of roles. AC-II is part of the anthrax bacterium's killing mechanism, for example, while AC-III triggers adrenaline release in humans.
Shape plays an essential role in determining the biological function of a protein, but it's very difficult to determine for such large molecules. Three-dimensional structures are known for only two other forms of AC. The NIST experiments revealed that AC-IV has a shape completely different from the other two known shapes. AC-IV folds into a rare form of a barrel-like shape previously seen in only three other unrelated proteins.
The purpose of AC-IV in plague is not well understood, but it may play a role in disrupting cell processes in the infected host. Plague is not as common as it was in the Middle Ages, when it killed millions, but the World Health Organization still logs about 1,000 to 3,000 cases a year, an average of 10 to 15 in the United States. It is rated as a highest category biothreat agent by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. Fundamental molecular data on this enzyme and its various forms may be critical to the development of defenses against plague and other pathogens, including Bacillus anthracis (Anthrax) and Bordetella pertussis (Whooping cough). Beyond that, structural and functional studies of AC-IV, with its unusual shape, may lead to deeper understanding of the cAMP signaling mechanism and other fundamental cellular processes.
