8GJF

afupcna bound with peptide mimetic

8GJF の概要

• エントリーDOI: 10.2210/pdb8gjf/pdb
• 分子名称: Proliferating cell nuclear antigen, LYS-ARG-ARG-GLN-THR-SER-MET-THR-ASP-PHE-TYR-HIS-SER-LYS-ARG (3 entities in total)
• 機能のキーワード: pcna, dna replication, peptide mimetic, replication
• 由来する生物種: Aspergillus fumigatus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 90039.55

構造登録者

Vandborg, B.,Bruning, J.B. (登録日: 2023-03-15, 公開日: 2024-01-24)

主引用文献

Vandborg, B.C.,Horsfall, A.J.,Pederick, J.L.,Abell, A.D.,Bruning, J.B.
Towards a High-Affinity Peptidomimetic Targeting Proliferating Cell Nuclear Antigen from Aspergillus fumigatus.
J Fungi, 9:-, 2023

PubMed Abstract: Invasive fungal infections (IFIs) are prevalent in immunocompromised patients. Due to alarming levels of increasing resistance in clinical settings, new drugs targeting the major fungal pathogen are required. Attractive drug targets are those involved in essential processes like DNA replication, such as proliferating cell nuclear antigens (PCNAs). PCNA has been previously studied in cancer research and presents a viable target for antifungals. Human PCNA interacts with the p21 protein, outcompeting binding proteins to halt DNA replication. The affinity of p21 for hPCNA has been shown to outcompete other associating proteins, presenting an attractive scaffold for peptidomimetic design. p21 has no homolog to our knowledge, yet our group has previously demonstrated that human p21 can interact with PCNA (afumPCNA). This suggests that a p21-based inhibitor could be designed to outcompete the native binding partners of afumPCNA to inhibit fungal growth. Here, we present an investigation of extensive structure-activity relationships between designed p21-based peptides and afumPCNA and the first crystal structure of a p21 peptide bound to afumPCNA, demonstrating that the replication model uses a PIP-box sequence as the method for binding to afumPCNA. These results inform the new optimized secondary structure design of a potential peptidomimetic inhibitor of afumPCNA.

PubMed: 37998903
DOI: 10.3390/jof9111098

実験手法

X-RAY DIFFRACTION (2 Å)