4AJE
rat LDHA in complex with 2-(4-bromophenoxy)propanedioic acid
Summary for 4AJE
| Entry DOI | 10.2210/pdb4aje/pdb |
| Related | 4AJ1 4AJ2 4AJ4 4AJH |
| Descriptor | L-LACTATE DEHYDROGENASE A CHAIN, 2-(4-BROMANYLPHENOXY)PROPANEDIOIC ACID, MALONATE ION, ... (5 entities in total) |
| Functional Keywords | oxidoreductase-inhibitor complex, fragment based lead generated inhibitors, oxidoreductase/inhibitor |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm: P04642 |
| Total number of polymer chains | 4 |
| Total formula weight | 147339.68 |
| Authors | Tucker, J.A.,Brassington, C.,Hassall, G.,Vogtherr, M.,Ward, R.,Tart, J.,Davies, G.,Pearson, S. (deposition date: 2012-02-16, release date: 2012-03-21, Last modification date: 2024-05-01) |
| Primary citation | Ward, R.,Brassington, C.,Breeze, A.L.,Caputo, A.,Critchlow, S.,Davies, G.,Goodwin, L.,Hassall, G.,Greenwood, R.,Holdgate, G.,Mrosek, M.,Norman, R.A.,Pearson, S.,Tart, J.,Tucker, J.A.,Vogtherr, M.,Whittaker, D.,Wingfield, J.,Winter, J.,Hudson, K. The Design and Synthesis of Novel Lactate Dehydrogenase a Inhibitors by Fragment-Based Lead Generation J.Med.Chem., 55:3285-, 2012 Cited by PubMed Abstract: Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work. PubMed: 22417091DOI: 10.1021/JM201734R PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.35 Å) |
Structure validation
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