Structure of key enzyme in plague bacterium found
鼠疫细菌中关键酶的结构已被发现
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.
国家标准与技术研究所（NISI）的研究者们已经解析了导致鼠疫的细菌中关键酶的结构，发现它有着极为不寻常的构象。这一结果会使我们搞清楚该细菌致死性之所在以及一些基础的细胞信号传导步骤。
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.
NISI研究小组鉴定了第四类腺嘌呤环化酶（AC-IV）的三维构象。这种酶存在于鼠疫细菌——耶尔森氏鼠疫杆菌中,科学家们将这种酶纯化及结晶，在生物技术高级研究中心利用x衍射晶体学的方法解析了它的构象。它合成环磷酸腺苷（cAMP）,这是一种重要的信号分子，会触发一系列细胞过程。目前已知六类腺嘌呤环化酶，这些酶发挥的广泛的作用。第二类AC是炭疽细菌致死机制的一部分，而第三类AC则触发了人体内肾上腺素的释放。
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.
构象对决定一个蛋白的生物学功能发挥了决定性作用，但对于这样一种大分子而言鉴定其构象是一件相当困难的事情。AC的三维构象已知存在两种形式。NISI的实验发现了AC-IV存在着与前两者完全不同的构象。AC-IV以一种相当罕见的类似桶状的结构加以折叠，这种形式此前仅在三种无关蛋白中存在。
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.
AC-IV在鼠疫中的作用尚未完全明了，但已知它在被感染的宿主中发挥着破坏细胞过程的角色。现在鼠疫不像中世纪时那样流行，当时它杀死了数以百万计的人。但目前世界卫生组织每年仍有1000~3000的病例报告，平均10~15例发生在美国。国家疾病预防控制中心和国家过敏与传染疾病研究所把鼠疫细菌列在最高等级生物威胁因子目录当中。关于这个酶的基础分子数据在研发有关鼠疫及其他病原体如炭疽菌，博尔代百日咳菌的抵御措施方面非常重要。不仅如此，关于AC-IV的结构和功能及其不同寻常的构象研究将使我们更深得理解cAMP的信号机制和其他基本的细胞过程。
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Details of the structure of AC-IV are published in: D.T. Gallagher, N. Smith, S-K Kim, A. Heroux, H. Robinson and P. Reddy. Structure of the class IV adenylyl cyclase reveals a novel fold. J. Mol. Biol., In Press, Corrected Proof, Available online 14 Aug. 2006.
关于AC-IV结构的细节发表在：D.T. Gallagher, N. Smith, S-K Kim, A. Heroux, H. Robinson and P. Reddy. Structure of the class IV adenylyl cyclase reveals a novel fold. J. Mol. Biol., In Press, Corrected Proof, Available online 14 Aug. 2006.
