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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美國標準技術(shù)研究院（NIST）已經(jīng)破解了來源于鼠疫桿菌的一種關(guān)鍵酶的結(jié)構(gòu),，并且發(fā)現(xiàn)它具有一種非常特別的構(gòu)型,。這些結(jié)果揭示出了這種細菌毒性機制和相關(guān)的基礎(chǔ)細胞信號過程,。
NIST研究組確定出了IV腺嘌呤環(huán)化酶（AC-IV）的三維結(jié)構(gòu)，這種酶存在于曾引發(fā)人類瘟疫的鼠疫桿菌（Yersinia pestis）中,。通過提純和結(jié)晶這種蛋白質(zhì),，然后用X射線晶體衍射技術(shù),，研究人員最終破譯了這種關(guān)鍵酶的構(gòu)型,。這種酶能夠合成環(huán)形AMP(cAMP)——一種能引發(fā)多種細胞過程的重要信號分子。目前已經(jīng)知道了六種類型的AC,，并且起到多種功能。
在決定一個蛋白質(zhì)的生物功能時,，蛋白質(zhì)的形狀起到?jīng)Q定性作用,，但是由于這種酶分子很大，因此形狀的確定很困難,。NIST的實驗表明AC-IV的形狀與其他已知結(jié)構(gòu)的AC（AC-II和AC-III）完全不同,。AC-IV折疊成一種罕見的水桶狀。此前,，這種形狀只在另外三種不相關(guān)的蛋白質(zhì)發(fā)現(xiàn)過,。
雖然AC-IV在鼠疫中的作用機制還不是很清楚，但是研究人員推測它可能干擾被感染寄主的細胞過程,。這種酶的基礎(chǔ)分子信息和它的不同構(gòu)型信息可能是人類開發(fā)應(yīng)對這種瘟疫和其他病原物的關(guān)鍵,。
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.
