4MMM

Human Pdrx5 complex with a ligand BP7

Summary for 4MMM

• Entry DOI: 10.2210/pdb4mmm/pdb
• Related: 4K7I 4K7N 4K7O
• Descriptor: Peroxiredoxin-5, mitochondrial, 1,1'-BIPHENYL-3,4-DIOL (3 entities in total)
• Functional Keywords: enzyme, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Mitochondrial: Mitochondrion. Isoform Cytoplasmic+peroxisomal: Cytoplasm: P30044
• Total number of polymer chains: 4
• Total formula weight: 71714.31

Authors

Guichou, J.F. (deposition date: 2013-09-09, release date: 2014-07-30, Last modification date: 2024-03-20)

Primary citation

Aguirre, C.,Brink, T.T.,Guichou, J.F.,Cala, O.,Krimm, I.
Comparing Binding Modes of Analogous Fragments Using NMR in Fragment-Based Drug Design: Application to PRDX5
Plos One, 9:e102300-e102300, 2014

PubMed Abstract: Fragment-based drug design is one of the most promising approaches for discovering novel and potent inhibitors against therapeutic targets. The first step of the process consists of identifying fragments that bind the protein target. The determination of the fragment binding mode plays a major role in the selection of the fragment hits that will be processed into drug-like compounds. Comparing the binding modes of analogous fragments is a critical task, not only to identify specific interactions between the protein target and the fragment, but also to verify whether the binding mode is conserved or differs according to the fragment modification. While X-ray crystallography is the technique of choice, NMR methods are helpful when this fails. We show here how the ligand-observed saturation transfer difference (STD) experiment and the protein-observed 15N-HSQC experiment, two popular NMR screening experiments, can be used to compare the binding modes of analogous fragments. We discuss the application and limitations of these approaches based on STD-epitope mapping, chemical shift perturbation (CSP) calculation and comparative CSP sign analysis, using the human peroxiredoxin 5 as a protein model.

PubMed: 25025339
DOI: 10.1371/journal.pone.0102300

Experimental method

X-RAY DIFFRACTION (1.47 Å)