3Q4L

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

3Q4L の概要

• エントリーDOI: 10.2210/pdb3q4l/pdb
• 関連するPDBエントリー: 1OK7 3D1E 3D1F 3D1G 3Q4J 3Q4K
• 関連するBIRD辞書のPRD_ID: PRD_001111
• 分子名称: DNA polymerase III subunit beta, peptide ligand, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Cytoplasm: P0A988
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83107.74

構造登録者

Wolff, P.,Olieric, V.,Briand, J.P.,Chaloin, O.,Dejaegere, A.,Dumas, P.,Ennifar, E.,Guichard, G.,Wagner, J.,Burnouf, D. (登録日: 2010-12-23, 公開日: 2011-12-28, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)