9MT9

Candida albicans Hsp90 nucleotide binding domain in complex with BTB10184

9MT9 の概要

• エントリーDOI: 10.2210/pdb9mt9/pdb
• 分子名称: Heat shock protein 90 homolog, 4-(4-hydroxyphenyl)sulfanylphenol (3 entities in total)
• 機能のキーワード: inhibitor complex, chaperone, chaperone-inhibitor complex, chaperone/inhibitor
• 由来する生物種: Candida albicans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26569.11

構造登録者

Kowalewski, M.E.,Redinbo, M.R. (登録日: 2025-01-10, 公開日: 2025-06-04)

主引用文献

Kowalewski, M.E.,Zagler, S.,Redinbo, M.R.
Structural Insights into Selectively Targeting Candida albicans Hsp90.
Biochemistry, 2025

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: 40397669
DOI: 10.1021/acs.biochem.5c00015

実験手法

X-RAY DIFFRACTION (1.78 Å)