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Publication Abstract from PubMed

Protein-protein 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-LM 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.

Structural and Thermodynamic Dissection of Linear Motif Recognition by the E. coli Sliding Clamp.,Yin Z, Kelso MJ, Beck JL, Oakley AJ J Med Chem. 2013 Nov 14;56(21):8665-73. doi: 10.1021/jm401118f. Epub 2013 Oct 22. PMID:24090409^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.