4BPM
Crystal structure of a human integral membrane enzyme
Summary for 4BPM
| Entry DOI | 10.2210/pdb4bpm/pdb |
| Related | 4BPD |
| Descriptor | PROSTAGLANDIN E SYNTHASE, FUSION PEPTIDE, GLUTATHIONE, 2-[[2,6-bis(chloranyl)-3-[(2,2-dimethylpropanoylamino)methyl]phenyl]amino]-1-methyl-6-(2-methyl-2-oxidanyl-propoxy)-N-[2,2,2-tris(fluoranyl)ethyl]benzimidazole-5-carboxamide, ... (4 entities in total) |
| Functional Keywords | isomerase, cancer, drug target, in meso crystallization, inflammation, inhibitor, leukotriene c4 synthase, lipid metabolism, membrane-associated proteins in eicosanoid and glutathione metabolism, mapag, membrane protein, mpges1, pain, microcrystal, anomalous dispersion, sulfur-sad, s-sad |
| Biological source | HOMO SAPIENS More |
| Total number of polymer chains | 1 |
| Total formula weight | 21286.73 |
| Authors | Li, D.,Wang, M.,Olieric, V.,Caffrey, M. (deposition date: 2013-05-27, release date: 2014-04-16, Last modification date: 2024-05-08) |
| Primary citation | Li, D.,Howe, N.,Dukkipati, A.,Shah, S.T.A.,Bax, B.D.,Edge, C.,Bridges, A.,Hardwicke, P.,Singh, O.M.P.,Giblin, G.,Pautsch, A.,Pfau, R.,Schnapp, G.,Wang, M.,Olieric, V.,Caffrey, M. Crystallizing Membrane Proteins in the Lipidic Mesophase. Experience with Human Prostaglandin E2 Synthase 1 and an Evolving Strategy. Cryst.Growth Des., 14:2034-, 2014 Cited by PubMed Abstract: The lipidic mesophase or in meso method for crystallizing membrane proteins has several high profile targets to its credit and is growing in popularity. Despite its success, the method is in its infancy as far as rational crystallogenesis is concerned. Consequently, significant time, effort, and resources are still required to generate structure-grade crystals, especially with a new target type. Therefore, a need exists for crystallogenesis protocols that are effective with a broad range of membrane protein types. Recently, a strategy for crystallizing a prokaryotic α-helical membrane protein, diacylglycerol kinase (DgkA), by the in meso method was reported (Cryst. Growth. Des.2013, 14, 2846-2857). Here, we describe its application to the human α-helical microsomal prostaglandin E2 synthase 1 (mPGES1). While the DgkA strategy proved useful, significant modifications were needed to generate structure-quality crystals of this important therapeutic target. These included protein engineering, using an additive phospholipid in the hosting mesophase, performing multiple rounds of salt screening, and carrying out trials at 4 °C in the presence of a tight binding ligand. The crystallization strategy detailed here should prove useful for generating structures of other integral membrane proteins by the in meso method. PubMed: 24803849DOI: 10.1021/CG500157X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.08 Å) |
Structure validation
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