7H65

THE 1.8 A CRYSTAL STRUCTURE OF HUMAN CHYMASE IN COMPLEX WITH N-[1-[2-[[2-hydroxy-3-methyl-3-(4-methylphenyl)-4-oxocyclobuten-1-yl]-phenylmethyl]-6-methyl-1H-indol-3-yl]-2-methylpropan-2-yl]acetamide

This is a non-PDB format compatible entry.

Summary for 7H65

• Entry DOI: 10.2210/pdb7h65/pdb
• Group deposition: A set of chymase crystal structures for D3R plus two CatG off-target structures (G_1002292)
• Descriptor: Chymase, ZINC ION, N-(1-{2-[(S)-[(3S)-2-hydroxy-3-methyl-3-(4-methylphenyl)-4-oxocyclobut-1-en-1-yl](phenyl)methyl]-6-methyl-1H-indol-3-yl}-2-methylpropan-2-yl)acetamide, ... (5 entities in total)
• Functional Keywords: human chymase, serine proteinase, chymase, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 25775.25

Authors

Banner, D.W.,Benz, J.M.,Schlatter, D.,Hilpert, H. (deposition date: 2024-04-19, release date: 2025-03-05, Last modification date: 2026-03-04)

Primary citation

Tosstorff, A.,Rudolph, M.G.,Benz, J.,Kuhn, B.,Kramer, C.,Sharpe, M.,Huang, C.Y.,Metz, A.,Hazemann, J.,Ritz, D.,Sweeney, A.M.,Gilson, M.K.
The CASP 16 Experimental Protein-Ligand Datasets.
Proteins, 94:79-85, 2026

PubMed Abstract: This paper presents the experimental protein-ligand datasets used as benchmarks in the CASP 16 blind prediction experiment-the first CASP round to incorporate targets from pharmaceutical discovery projects. We have assembled and characterized protein-ligand complexes for four proteins that are known or candidate drug targets: human chymase, human cathepsin G, human autotaxin, and the SARS-CoV-2 main protease. The collection encompasses over 200 co-crystal structures at resolutions better than 2.7 Å, paired with binding affinity measurements for approximately 160 compounds covering a broad affinity range (nanomolar to high micromolar). These data enabled the CASP16 pose-prediction and affinity-prediction challenges. Many systems feature potentially challenging characteristics, including chymase's electropositive surface and acidic ligands, which require proper handling of titratable ligand groups; autotaxin complexes with and without zinc coordination; and a SARS-CoV-2 protease crystal form exhibiting an unusually open active site conformation. We describe the experimental approaches-from protein production and crystallization to binding assay development-that yielded these reference data. Contributed by scientists at F. Hoffmann-La Roche and Idorsia Pharmaceuticals, these datasets represent actual drug discovery projects and therefore provide a realistic testbed for assessing how computational methods perform on pharmaceutically relevant targets. An accompanying paper in the present special journal issue provides a comprehensive assessment of the pose and affinity predictions for these pharmaceutical protein-ligand systems.

PubMed: 41040057
DOI: 10.1002/prot.70053

Experimental method

X-RAY DIFFRACTION (1.8 Å)