3Q4J

Structure of a small peptide ligand bound to E.coli DNA sliding clamp

Summary for 3Q4J

• Entry DOI: 10.2210/pdb3q4j/pdb
• Related: 1OK7 2POL 3D1E 3D1F 3D1G 3Q4K 3Q4L
• Descriptor: DNA polymerase III subunit beta, peptide ligand (3 entities in total)
• Functional Keywords: dna polymerase, sliding clamp, processivity factors, ligand binding, dna replication, dna-directed dna polymerase, nucleotidyltransferase, transferase, transferase-peptide complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm: P0A988
• Total number of polymer chains: 11
• Total formula weight: 247086.84

Authors

Wolff, P.,Olieric, V.,Briand, J.P.,Chaloin, O.,Dejaegere, A.,Dumas, P.,Ennifar, E.,Guichard, G.,Wagner, J.,Burnouf, D. (deposition date: 2010-12-23, release date: 2011-12-28, Last modification date: 2024-11-06)

Primary citation

Wolff, P.,Olieric, V.,Briand, J.P.,Chaloin, O.,Dejaegere, A.,Dumas, P.,Ennifar, E.,Guichard, G.,Wagner, J.,Burnouf, D.Y.
Structure-based design of short peptide ligands binding onto the E. coli processivity ring.
J.Med.Chem., 54:4627-4637, 2011

PubMed Abstract: The multimeric DNA sliding clamps confer high processivity to replicative DNA polymerases and are also binding platforms for various enzymes involved in DNA metabolism. These enzymes interact with the clamp through a small peptide that binds into a hydrophobic pocket which is a potential target for the development of new antibacterial compounds. Starting from a generic heptapeptide, we used a structure-based strategy to improve the design of new peptide ligands. Chemical modifications at specific residues result in a dramatic increase of the interaction as measured by SPR and ITC. The affinity of our best hits was improved by 2 orders of magnitude as compared to the natural ligand, reaching 10(-8) M range. The molecular basis of the interactions was analyzed by solving the co-crystal structures of the most relevant peptides bound to the clamp and reveals how chemical modifications establish new contacts and contributes to an increased affinity of the ligand.

PubMed: 21619076
DOI: 10.1021/jm200311m

Experimental method

X-RAY DIFFRACTION (2.3 Å)