9PRE
Crystal structure of oxidised E.coli DsbA in complex with propiolic acid
This is a non-PDB format compatible entry.
Summary for 9PRE
| Entry DOI | 10.2210/pdb9pre/pdb |
| Descriptor | Thiol:disulfide interchange protein DsbA, ZINC ION, 3-{3-[(5-methyl-1,2-oxazole-3-carbonyl)amino]phenyl}prop-2-ynoic acid, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, oxidoreductase inhibitor, dsba, bacteria, enzyme |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 21697.14 |
| Authors | Balaji, G.R.,Ilyichova, O.V.,Tasdan, Y.,Akhtar, N.,Scanlon, M.J. (deposition date: 2025-07-24, release date: 2026-03-25) |
| Primary citation | Tasdan, Y.,Balaji, G.R.,Davidson, J.,Akhtar, N.,Ilyichova, O.,Guetzoyan, L.J.,Chandrashekaran, I.R.,Alwan, W.,Cobb, H.,Gunzburg, M.J.,Hasanzada, A.,Roughley, S.D.,Murray, J.B.,Thai, V.C.,Cliff, T.,Kahler, C.M.,Mohanty, B.,Capuano, B.,Doak, B.C.,Scanlon, M.J. Exploiting a Cryptic Pocket in DsbA through Structure-Guided Parallel Synthesis and Direct-to-Biology Screening. J.Med.Chem., 2026 Cited by PubMed Abstract: Antibacterial resistance is a major global health problem, causing an increasing number of deaths worldwide. DsbA, a bacterial oxidoreductase enzyme, is pivotal for the correct folding and activity of virulence factors in bacteria. Inhibiting DsbA presents a promising avenue for developing antivirulence compounds and combating bacterial resistance. The enzyme's structure features two ligand-binding sites: a hydrophobic groove that is the binding site for natural peptide substrates and a "cryptic pocket" enclosed within the protein, which has recently been identified as a target for ligand design. In this study, we report the elaboration of a fragment from within the enclosed cryptic pocket into the hydrophobic groove of DsbA, using X-ray crystallography-guided structure-based design and parallel synthesis coupled with crude reaction mixture screening (direct-to-biology). This effort yielded the most potent small-molecule DsbA inhibitors reported to date and exemplifies a productive strategy for exploiting a cryptic pocket for drug development. PubMed: 41789772DOI: 10.1021/acs.jmedchem.5c03004 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.68 Å) |
Structure validation
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