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Structural and thermodynamic dissection of linear motif recognition by the E. coli sliding clamp

Journal Article


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Abstract


  • 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.

Publication Date


  • 2013

Citation


  • Yin, Z., Kelso, M. J., Beck, J. L. & Oakley, A. J. (2013). Structural and thermodynamic dissection of linear motif recognition by the E. coli sliding clamp. Journal of Medicinal Chemistry, 56 (21), 8665-8673.

Scopus Eid


  • 2-s2.0-84887953554

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2262&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1244

Number Of Pages


  • 8

Start Page


  • 8665

End Page


  • 8673

Volume


  • 56

Issue


  • 21

Abstract


  • 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.

Publication Date


  • 2013

Citation


  • Yin, Z., Kelso, M. J., Beck, J. L. & Oakley, A. J. (2013). Structural and thermodynamic dissection of linear motif recognition by the E. coli sliding clamp. Journal of Medicinal Chemistry, 56 (21), 8665-8673.

Scopus Eid


  • 2-s2.0-84887953554

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2262&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1244

Number Of Pages


  • 8

Start Page


  • 8665

End Page


  • 8673

Volume


  • 56

Issue


  • 21