9SDI

FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH 6-(1H-Pyrazol-4-yl)-nicotinic acid

This is a non-PDB format compatible entry.

Summary for 9SDI

• Entry DOI: 10.2210/pdb9sdi/pdb
• Descriptor: Focal adhesion kinase 1, SULFATE ION, 6-(1~{H}-pyrazol-4-yl)pyridine-3-carboxylic acid, ... (4 entities in total)
• Functional Keywords: protein tyrosine kinase, transferase, atp binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 64393.14

Authors

Musil, D. (deposition date: 2025-08-14, release date: 2025-12-31, Last modification date: 2026-01-14)

Primary citation

F Malta, C.,O Silva, D.,Gradler, U.,M F Sousa, P.,Musil, D.,Schwarz, D.,Bomke, J.,M Bandeiras, T.,Bortoluzzi, A.
Pushing the limits of hydrogen/deuterium exchange mass spectrometry to study protein:fragment low affinity interactions.
Commun Chem, 8:405-405, 2025

PubMed Abstract: Characterization of protein-ligand interactions is essential for the pre-clinical development of drug candidates and Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS) has emerged as a valuable tool in this process. HDX-MS has predominantly been employed with high affinity compounds with only a few examples of its application for weaker binders such as fragments. Nevertheless, HDX-MS usage could be instrumental in Fragment-Based Drug Discovery (FBDD) programs. In this work, the drug-target protein Cyclophilin D (CypD) was used as a model to explore the boundaries of fragments binding characterization by HDX-MS (fHDX-MS). We performed a systematic study on the optimal conditions for fHDX-MS execution and found that fragments with binding affinities in the double-digit mM range are still amenable to fHDX-MS. We observed that, despite the intrinsic low resolution of HDX-MS, fragments binding sites that partially overlap can still be distinguished. Overall, this study shows that fHDX-MS can be a useful method for FBDD.

PubMed: 41429916
DOI: 10.1038/s42004-025-01787-6

Experimental method

X-RAY DIFFRACTION (2.53 Å)