- 期刊
原核生物IIA型DNA拓撲異構酶辨認受質幾何構形機制之探討
On the Recognition and Regulation of DNA Topology by Prokaryotic Type IIA Topoisomerases
摘要
在原核生物中，移除染色體DNA之纏繞與套環、以及維持DNA 拓撲狀態恆定的重要工作，主要 係由DNA gyrase 與topoisomerase IV (TopoIV)這二個IIA 型DNA 拓撲異構所負責。有趣的是，雖然二 者的胺基酸序列非常相似，但其活性與生物功能卻截然不同；DNA gyrase 以其能在DNA 上引入負超螺旋 的活性，使得DNA 複製與轉錄能夠順利進行，而TopoIV 則以移除正超螺旋及套環為主，為同源染色體 分離時不可或缺的蛋白。為何這兩個同源且高度類似的酵素在活性及受質選擇上有如此的差異呢？最近的 研究顯示，DNA gyrase 與TopoIV 之C 末端區，極可能是造成其功能分歧的主因之一。因此本文首先將介 紹並比較其C 末端區的晶體結構，再藉由此差異探討二者辨識及調節DNA 受質之拓撲結構的機制。
並列摘要
In bacteria, the resolution of DNA entanglements and maintenance of topological homeostasis are largely handled by two essential type IIA topoisomerases, DNA gyrase and topoisomerase IV (TopoIV). Interestingly, although DNA gyrase and TopoIV share a high degree of similarity, they possess distinct cellular functions and thus cannot complement each other in vivo. DNA gyrase supports replication and transcription with its unique negative supercoiling activity, whereas TopoIV preferentially relaxes (+) supercoils and is a decatenating enzyme required for chromosome segregation. How do these two highly similar enzymes diverge in catalytic activities and substrate specificities? Recent studies hint that the functional differences between them can be attributed at least in part to their respective C-terminal domains (CTDs). In this review, the structural differences between the gyrase-CTD and TopoIV-CTD will be described, and how prokaryotic type IIA enzymes recognize and regulate substrate DNA topology will be discussed.