7AZL

DNA polymerase sliding clamp from Escherichia coli with peptide 38 bound

7AZL の概要

• エントリーDOI: 10.2210/pdb7azl/pdb
• 分子名称: Beta sliding clamp, Peptide 38, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: antibacterial drug, dna binding protein
• 由来する生物種: Escherichia coli 2-427-07_S4_C3; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 175075.18

構造登録者

Monsarrat, C.,Compain, G.,Andre, C.,Martiel, I.,Engilberge, S.,Olieric, V.,Wolff, P.,Brillet, K.,Landolfo, M.,Silva da Veiga, C.,Wagner, J.,Guichard, G.,Burnouf, D.Y. (登録日: 2020-11-16, 公開日: 2021-12-01, 最終更新日: 2024-07-10)

主引用文献

Monsarrat, C.,Compain, G.,Andre, C.,Engilberge, S.,Martiel, I.,Olieric, V.,Wolff, P.,Brillet, K.,Landolfo, M.,Silva da Veiga, C.,Wagner, J.,Guichard, G.,Burnouf, D.Y.
Iterative Structure-Based Optimization of Short Peptides Targeting the Bacterial Sliding Clamp.
J.Med.Chem., 64:17063-17078, 2021

PubMed Abstract: The bacterial DNA sliding clamp (SC), or replication processivity factor, is a promising target for the development of novel antibiotics. We report a structure-activity relationship study of a new series of peptides interacting within the SC (SC) binding pocket. Various modifications were explored including N-alkylation of the peptide bonds, extension of the N-terminal moiety, and introduction of hydrophobic and constrained residues at the C-terminus. In each category, single modifications were identified that increased affinity to SC. A combination of such modifications yielded in several cases to a substantially increased affinity compared to the parent peptides with in the range of 30-80 nM. X-ray structure analysis of 11 peptide/SC co-crystals revealed new interactions at the peptide-protein interface (i.e., stacking interactions, hydrogen bonds, and hydrophobic contacts) that can account for the improved binding. Several compounds among the best binders were also found to be more effective in inhibiting SC-dependent DNA synthesis.

PubMed: 34806883
DOI: 10.1021/acs.jmedchem.1c00918

実験手法

X-RAY DIFFRACTION (2.42 Å)