The molecular details of the bacterial helicase-primase complex

DNA复制是所有生物体最基本的功能之一。了解细菌DNA复制的基本作用机制不仅对将我们的发现推广到更复杂的真核生物至关重要，而且对设计新的抗菌素在我们对抗抗生素耐药性的斗争中至关重要。解旋酶-引物酶复合体是一种普遍存在的细菌复合体。我们目前对其功能的分子基础了解甚少。最近我们已经解决了B. stearothermophilus引物酶蛋白解旋酶相互作用结构域的结构，我们发现这个结构域在结构上与解旋酶本身的n端结构域同源。这是一个令人惊讶的发现，它使我们提出了一个模型，试图解释细菌解旋酶-引物酶复合物的功能。我们现在正在寻求资金，通过一系列的生化实验来直接测试这个模型的有效性。这项研究的结果将使我们能够了解这个重要复合体的分子细节，并为设计新的抗菌药物铺平道路，这些药物将针对这个复合体，从而促进细菌DNA的复制。

DNA replication is one of the most fundamental functions of all living organisms. Understanding the basic mechanisms of action of bacterial DNA replication will be essential not only to extrapolate our findings to the more complex eukaryotic organisms, but also to design new antibacterials in our fight against antibiotic resistance. The helicase-primase complex is a ubiquitous and essential bacterial complex. Our current understanding of the molecular basis of its functions is poorly understood. Recently we have solved the structure of the helicase-interacting domain of the B. stearothermophilus primase protein and we discovered that this domain is structurally homologous to the N-terminal domain of the helicase itself. This was a surprising discovery and one that led us to propose a model to try and explain how the bacterial helicase-primase complex functions. We are now seeking funding to test directly the validity of this model with a series of biochemical experiments. The results of this research will enable us to understand the molecular details of this important complex and will pave the way for the design of new antibacterial drugs that will target this complex and thus bacterial DNA replication.