9TM1

Crystal structure of bromodomain from Plasmodium falciparum GCN5 complexed with a ligand

This is a non-PDB format compatible entry.

Summary for 9TM1

• Entry DOI: 10.2210/pdb9tm1/pdb
• Descriptor: histone acetyltransferase, N-[(2S)-3-[2,4-bis(oxidanylidene)pyrimidin-1-yl]-1-(methylamino)-1-oxidanylidene-propan-2-yl]-6-methoxy-3H-imidazo[4,5-b]pyridine-7-carboxamide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: inhibitor, bromodomain, transferase
• Biological source: Plasmodium falciparum 3D7
• Total number of polymer chains: 3
• Total formula weight: 39064.92

Authors

McMillan, J.,Postis, V.,Masson, G. (deposition date: 2025-12-11, release date: 2026-04-08)

Primary citation

Lin, D.,Magalhaes, L.G.,McMillan, J.,Eadsforth, T.C.,Stewart, G.,Cartmill, K.R.,Postis, V.L.G.,Masson, G.R.
Residue-Level Determination of Small-Molecule-Protein Affinities by Hydrogen-Deuterium Exchange Mass Spectrometry.
J.Am.Soc.Mass.Spectrom., 2026

PubMed Abstract: Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) is an established tool in drug discovery, used to characterize target engagement and conformational dynamics, and frequently used in both biopharmaceutical and small molecule drug discovery. Conventional HDX-MS experiments are performed at saturating ligand concentrations to generate a binding "footprint", where decreased solvent exchange reflects a local structural stabilization or reduced solvent accessibility upon binding. Here, we present an extended HDX-MS and HDX-MS/MS titration workflow with electron capture dissociation (ECD) fragmentation capable of estimating apparent dissociation constants () at global, peptide, and single amino acid resolution by fitting uptake-concentration relationships under EX2 exchange and Langmuir binding assumptions. The ability to determine affinity constants in a spatially resolved manner combined with the automation available in HDX-MS sample handling and data analysis enables quantitative mapping of ligand-protein interactions and provides a scalable approach for structure-activity relationship studies in drug discovery.

PubMed: 41915381
DOI: 10.1021/jasms.6c00020

Experimental method

X-RAY DIFFRACTION (1.8 Å)