9MT9
Candida albicans Hsp90 nucleotide binding domain in complex with BTB10184
Summary for 9MT9
| Entry DOI | 10.2210/pdb9mt9/pdb |
| Descriptor | Heat shock protein 90 homolog, 4-(4-hydroxyphenyl)sulfanylphenol (3 entities in total) |
| Functional Keywords | inhibitor complex, chaperone, chaperone-inhibitor complex, chaperone/inhibitor |
| Biological source | Candida albicans |
| Total number of polymer chains | 1 |
| Total formula weight | 26569.11 |
| Authors | |
| Primary citation | Kowalewski, M.E.,Zagler, S.,Redinbo, M.R. Structural Insights into Selectively Targeting Candida albicans Hsp90. Biochemistry, 2025 Cited by PubMed Abstract: The threat of drug-resistant pathogens continues to rise and underscores the need for new antimicrobial and antifungal strategies. Diverse chemical scaffolds have been shown with high affinity to bind the human heat-shock protein Hsp90. Orthologous proteins are present in microbial pathogens and have been shown to be particularly abundant in these organisms, suggesting they may serve as therapeutic targets. Here, we examine the potency and selectivity of human Hsp90 ligands for their capacity to bind to the nucleotide binding domain of Hsp90 from the pathogenic fungi, . Using a series of biochemical, structural, and fragment and screening investigations, we define key chemical features that lead to effective Hsp90 (CaHsp90) binding. We support these studies with crystal structures of five diverse human Hsp90 ligands in complex with CaHsp90, as well as the structure of this protein with a nonhydrolyzable ATP analog. We demonstrate the structural basis for the selectivity of the human Hsp90 inhibitor TAS116 for CaHsp90, features that may be exploited in the future development of improved CaHsp90 inhibitors. PubMed: 40397669DOI: 10.1021/acs.biochem.5c00015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.78 Å) |
Structure validation
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