8E2O

Leveraging the Structure of DNAJA1 to Discover Novel Pancreatic Cancer Therapies

8E2O の概要

• エントリーDOI: 10.2210/pdb8e2o/pdb
• NMR情報: BMRB: 51532
• 分子名称: Isoform 2 of DnaJ homolog subfamily A member 1 (1 entity in total)
• 機能のキーワード: hsp40, chaperone, recombination
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12046.66

構造登録者

Roth, H.E.,Powers, R. (登録日: 2022-08-15, 公開日: 2022-11-09, 最終更新日: 2024-05-15)

主引用文献

Roth, H.E.,De Lima Leite, A.,Palermo, N.Y.,Powers, R.
Leveraging the Structure of DNAJA1 to Discover Novel Potential Pancreatic Cancer Therapies.
Biomolecules, 12:-, 2022

PubMed Abstract: Pancreatic cancer remains one of the deadliest forms of cancer with a 5-year survival rate of only 11%. Difficult diagnosis and limited treatment options are the major causes of the poor outcome for pancreatic cancer. The human protein DNAJA1 has been proposed as a potential therapeutic target for pancreatic cancer, but its cellular and biological functions remain unclear. Previous studies have suggested that DNAJA1's cellular activity may be dependent upon its protein binding partners. To further investigate this assertion, the first 107 amino acid structures of DNAJA1 were solved by NMR, which includes the classical J-domain and its associated linker region that is proposed to be vital to DNAJA1 functionality. The DNAJA1 NMR structure was then used to identify both protein and ligand binding sites and potential binding partners that may suggest the intracellular roles of DNAJA1. Virtual drug screenings followed by NMR and isothermal titration calorimetry identified 5 drug-like compounds that bind to two different sites on DNAJA1. A pull-down assay identified 8 potentially novel protein binding partners of DNAJA1. These proteins in conjunction with our previously published metabolomics study support a vital role for DNAJA1 in cellular oncogenesis and pancreatic cancer.

PubMed: 36291603
DOI: 10.3390/biom12101391

実験手法

SOLUTION NMR