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

Zhou Yin, Michael J. Kelso, Jennifer L. Beck, Aaron J. Oakley

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8665-8673
Number of pages9
JournalJournal of Medicinal Chemistry
Volume56
Issue number21
DOIs
StatePublished - Nov 14 2013
Externally publishedYes

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Thermodynamics
Dissection
Escherichia coli
Proteins
Dipeptides
Sexual Partners
Hydrogen Bonding

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Structural and thermodynamic dissection of linear motif recognition by the E. Coli sliding clamp. / Yin, Zhou; Kelso, Michael J.; Beck, Jennifer L.; Oakley, Aaron J.

In: Journal of Medicinal Chemistry, Vol. 56, No. 21, 14.11.2013, p. 8665-8673.

Research output: Contribution to journalArticle

Yin, Zhou ; Kelso, Michael J. ; Beck, Jennifer L. ; Oakley, Aaron J. / Structural and thermodynamic dissection of linear motif recognition by the E. Coli sliding clamp. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 21. pp. 8665-8673.
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