Structural and Thermodynamic Dissection of Linear Motif Recognition by the E. coli Sliding Clamp

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• 作者：Zhou Yin ; Michael J. Kelso ; Jennifer L. Beck ; Aaron J. Oakley
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：November 14, 2013
• 年：2013
• 卷：56
• 期：21
• 页码：8665-8673
• 全文大小：505K
• 年卷期：v.56,no.21(November 14, 2013)
• ISSN：1520-4804

文摘

Protein鈥損rotein interactions based on linear motif (LM) recognition play roles in many cell regulatory processes. The E. coli sliding clamp is a protein mediator of replisome formation, which uses a common surface pocket composed of two subsites (I and II) to interact with LMs in multiple binding partners. A structural and thermodynamic dissection of sliding clamp鈥揕M recognition has been performed, providing support for a sequential binding model. According to the model, a hydrophobic C-terminal LM dipeptide submotif acts as an anchor to establish initial contacts within subsite I, and this is followed by formation of a stabilizing hydrogen-bonding network between the flanking LM residues and subsite II. Differential solvation/desolvation during positioning of the submotifs is proposed as a driver for the sequential binding. Our model provides general insights into linear motif recognition and should guide the design of small-molecule inhibitors of the E. coli sliding clamp, an emerging antibacterial target.