7ODB
Crystal structure of bovine Hsc70(aa1-554)E213A/D214A in complex with triazine-derivative
Summary for 7ODB
| Entry DOI | 10.2210/pdb7odb/pdb |
| Related | 7O6R |
| Descriptor | Heat shock cognate 71 kDa protein, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, POTASSIUM ION, ... (6 entities in total) |
| Functional Keywords | chaperone |
| Biological source | Bos taurus (Bovine) |
| Total number of polymer chains | 1 |
| Total formula weight | 61714.82 |
| Authors | Zehe, M.,Grimm, C.,Sotriffer, C. (deposition date: 2021-04-29, release date: 2022-06-01, Last modification date: 2024-02-14) |
| Primary citation | Zehe, M.,Kehrein, J.,Schollmayer, C.,Plank, C.,Kovacs, H.,Merino Asumendi, E.,Holzgrabe, U.,Grimm, C.,Sotriffer, C. Combined In-Solution Fragment Screening and Crystallographic Binding-Mode Analysis with a Two-Domain Hsp70 Construct. Acs Chem.Biol., 2024 Cited by PubMed Abstract: Heat shock protein 70 (Hsp70) isoforms are key players in the regulation of protein homeostasis and cell death pathways and are therefore attractive targets in cancer research. Developing nucleotide-competitive inhibitors or allosteric modulators, however, has turned out to be very challenging for this protein family, and no Hsp70-directed therapeutics have so far become available. As the field could profit from alternative starting points for inhibitor development, we present the results of a fragment-based screening approach on a two-domain Hsp70 construct using in-solution NMR methods, together with X-ray-crystallographic investigations and mixed-solvent molecular dynamics simulations. The screening protocol resulted in hits on both domains. In particular, fragment binding in a deeply buried pocket at the substrate-binding domain could be detected. The corresponding site is known to be important for communication between the nucleotide-binding and substrate-binding domains of Hsp70 proteins. The main fragment identified at this position also offers an interesting starting point for the development of a dual Hsp70/Hsp90 inhibitor. PubMed: 38317495DOI: 10.1021/acschembio.3c00589 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.662 Å) |
Structure validation
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