Kobryn Kerri, Burgin Alex B, Chaconas George
Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
J Biol Chem. 2005 Jul 22;280(29):26788-95. doi: 10.1074/jbc.M504530200. Epub 2005 May 23.
ResT is the telomere resolvase of the spirochete Borrelia burgdorferi, the causative agent of Lyme disease. ResT is an essential cellular function that processes replication intermediates to produce linear replicons terminated by covalently closed hairpin telomeres. ResT generates these hairpin telomeres in a reaction with mechanistic similarities to those catalyzed by type IB topoisomerases and tyrosine recombinases. We report here, that like most of the tyrosine recombinases, ResT requires interprotomer communication, likely in an in-line synapse, to activate reaction chemistry. Unlike the tyrosine recombinases, however, we infer that the cleavage and strand transfer reactions on the two sides of the replicated telomere occur nearly simultaneously. Nonetheless, the chemical steps of the forward and reverse reactions performed by ResT can occur in a non-concerted fashion (i.e. events on the two sides of the replicated telomere can occur independently). We propose that uncoupling of reaction completion on the two sides of the substrate is facilitated by an early commitment to hairpin formation that is imposed by the precleavage action of the hairpin binding module of the ResT active site.
ResT是疏螺旋体伯氏疏螺旋体（莱姆病的病原体）的端粒解旋酶。ResT是一种基本的细胞功能，它处理复制中间体以产生由共价闭合的发夹端粒终止的线性复制子。ResT在与IB型拓扑异构酶和酪氨酸重组酶催化的反应具有机制相似性的反应中产生这些发夹端粒。我们在此报告，与大多数酪氨酸重组酶一样，ResT需要原聚体间通讯，可能是在线性突触中，以激活反应化学。然而，与酪氨酸重组酶不同的是，我们推断复制端粒两侧的切割和链转移反应几乎同时发生。尽管如此，ResT进行的正向和反向反应的化学步骤可以以非协同方式发生（即复制端粒两侧的事件可以独立发生）。我们提出，底物两侧反应完成的解偶联是由ResT活性位点的发夹结合模块的切割前作用施加的对发夹形成的早期承诺促进的。
