7ZGC
Structure of yeast Sec14p with NPPM481
Summary for 7ZGC
| Entry DOI | 10.2210/pdb7zgc/pdb |
| Descriptor | SEC14 cytosolic factor, (4-chloranyl-3-nitro-phenyl)-[4-(2-fluorophenyl)piperazin-1-yl]methanone, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | sec14p, nppm481, lipid binding protein |
| Biological source | Saccharomyces cerevisiae S288C |
| Total number of polymer chains | 1 |
| Total formula weight | 36506.62 |
| Authors | Hong, Z.,Johnen, P.,Schaaf, G.,Bono, F. (deposition date: 2022-04-03, release date: 2023-01-25, Last modification date: 2024-02-07) |
| Primary citation | Chen, X.R.,Poudel, L.,Hong, Z.,Johnen, P.,Katti, S.,Tripathi, A.,Nile, A.H.,Green, S.M.,Khan, D.,Schaaf, G.,Bono, F.,Bankaitis, V.A.,Igumenova, T.I. Mechanisms by which small molecules of diverse chemotypes arrest Sec14 lipid transfer activity. J.Biol.Chem., 299:102861-102861, 2023 Cited by PubMed Abstract: Phosphatidylinositol (PtdIns) transfer proteins (PITPs) enhance the activities of PtdIns 4-OH kinases that generate signaling pools of PtdIns-4-phosphate. In that capacity, PITPs serve as key regulators of lipid signaling in eukaryotic cells. Although the PITP phospholipid exchange cycle is the engine that stimulates PtdIns 4-OH kinase activities, the underlying mechanism is not understood. Herein, we apply an integrative structural biology approach to investigate interactions of the yeast PITP Sec14 with small-molecule inhibitors (SMIs) of its phospholipid exchange cycle. Using a combination of X-ray crystallography, solution NMR spectroscopy, and atomistic MD simulations, we dissect how SMIs compete with native Sec14 phospholipid ligands and arrest phospholipid exchange. Moreover, as Sec14 PITPs represent new targets for the development of next-generation antifungal drugs, the structures of Sec14 bound to SMIs of diverse chemotypes reported in this study will provide critical information required for future structure-based design of next-generation lead compounds directed against Sec14 PITPs of virulent fungi. PubMed: 36603766DOI: 10.1016/j.jbc.2022.102861 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.236 Å) |
Structure validation
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