The Missing Linker: A Dimerization Motif Located within Polyketide Synthase Modules

详细信息    查看全文

• 作者：Jianting Zheng ; Christopher D. Fage ; Borries Demeler ; David W. Hoffman ; Adrian T. Keatinge-Clay
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：June 21, 2013
• 年：2013
• 卷：8
• 期：6
• 页码：1263-1270
• 全文大小：539K
• 年卷期：v.8,no.6(June 21, 2013)
• ISSN：1554-8937

文摘

The dimerization of multimodular polyketide synthases is essential for their function. Motifs that supplement the contacts made by dimeric polyketide synthase enzymes have previously been characterized outside the boundaries of modules, at the N- and C-terminal ends of polyketide synthase subunits. Here we describe a heretofore uncharacterized dimerization motif located within modules. The dimeric state of this dimerization element was elucidated through the 2.6 脜 resolution crystal structure of a fragment containing a dimerization element and a ketoreductase. The solution structure of a standalone dimerization element was revealed by nuclear magnetic resonance spectroscopy to be consistent with that of the crystal structure, and its dimerization constant was measured through analytical ultracentrifugation to be 20 渭M. The dimer buries 990 脜² at its interface, and its C-terminal helices rigidly connect to ketoreductase domains to constrain their locations within a module. These structural restraints permitted the construction of a common type of polyketide synthase module.