5X74

The crystal Structure PDE delta in complex with compound (R, R)-1g

Summary for 5X74

• Entry DOI: 10.2210/pdb5x74/pdb
• Related: 5X72 5X73
• Descriptor: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta, (2R)-2-(2-fluorophenyl)-3-[2-[4-[(2R)-2-(2-fluorophenyl)-4-oxidanylidene-1,2-dihydroquinazolin-3-yl]piperidin-1-yl]ethyl]-1,2-dihydroquinazolin-4-one (3 entities in total)
• Functional Keywords: lipid binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytosol : O43924
• Total number of polymer chains: 1
• Total formula weight: 17992.62

Authors

Jiang, Y.,Zhuang, C.,Chen, L.,Wang, R.,Wang, F.,Sheng, C. (deposition date: 2017-02-23, release date: 2017-10-04, Last modification date: 2023-11-22)

Primary citation

Jiang, Y.,Zhuang, C.,Chen, L.,Lu, J.,Dong, G.,Miao, Z.,Zhang, W.,Li, J.,Sheng, C.
Structural Biology-Inspired Discovery of Novel KRAS-PDE delta Inhibitors
J. Med. Chem., 60:9400-9406, 2017

PubMed Abstract: Structural biology is a powerful tool for investigating the stereospecific interactions between a protein and its ligand. Herein, an unprecedented chiral binding pattern was observed for inhibitors of KRAS-PDEδ interactions. Virtual screening and X-ray crystallography studies revealed that two enantiomers of a racemic inhibitor could bind at different sites. Fragment-based drug design was used to identify highly potent PDEδ inhibitors that can be used as promising lead compounds for target validation and antitumor drug development.

PubMed: 28929751
DOI: 10.1021/acs.jmedchem.7b01243

Experimental method

X-RAY DIFFRACTION (2.25 Å)