4I15

Crystal structure of TbrPDEB1

4I15 の概要

• エントリーDOI: 10.2210/pdb4i15/pdb
• 分子名称: Class 1 phosphodiesterase PDEB1, ZINC ION, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: parasite pde, sleeping sickness, african trypanosomiasis, hydrolase
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77628.00

構造登録者

Wang, H.,Ke, H. (登録日: 2012-11-20, 公開日: 2013-03-13, 最終更新日: 2024-02-28)

主引用文献

Jansen, C.,Wang, H.,Kooistra, A.J.,de Graaf, C.,Orrling, K.M.,Tenor, H.,Seebeck, T.,Bailey, D.,de Esch, I.J.,Ke, H.,Leurs, R.
Discovery of Novel Trypanosoma brucei Phosphodiesterase B1 Inhibitors by Virtual Screening against the Unliganded TbrPDEB1 Crystal Structure.
J.Med.Chem., 56:2087-2096, 2013

PubMed Abstract: Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal structure of the catalytic domain of the unliganded TbrPDEB1 and its use for the in silico screening for new TbrPDEB1 inhibitors with novel scaffolds. The TbrPDEB1 crystal structure shows the characteristic folds of human PDE enzymes but also contains the parasite-specific P-pocket found in the structures of Leishmania major PDEB1 and Trypanosoma cruzi PDEC. The unliganded TbrPDEB1 X-ray structure was subjected to a structure-based in silico screening approach that combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. This approach identified six novel TbrPDEB1 inhibitors with IC50 values of 10-80 μM, which may be further optimized as potential selective TbrPDEB inhibitors.

PubMed: 23409953
DOI: 10.1021/jm3017877

実験手法

X-RAY DIFFRACTION (1.65 Å)