The Crystal Structure of the Hsp90-LA1011 Complex and the Mechanism by Which LA1011 May Improve the Prognosis of Alzheimer’s Disease
Abstract
:1. Introduction
2. Methods and Materials
2.1. Protein Purification
2.2. Crystallization and Refinement
2.3. Isothermal Titration Calorimetry
3. Results and Conclusions
3.1. The Crystal Structure of Hsp90-LA1011
3.2. LA1011 and FKBP51 Competitively Bind to Hsp90
3.3. Effects of LA1011 on the Binding of Other TPR-Domain-Containing Co-Chaperones of Hsp90
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Data Set (Highest Shell in Parentheses) | AutoPROC | STARANISO |
---|---|---|
a (Å) | 97.71 | |
b (Å) | 97.71 | |
c (Å) | 275.57 | |
α (°) | 90.0 | |
β (°) | 90.0 | |
γ (°) | 90.0 | |
Space group | P 41 21 21 | |
Wavelength (Å) | 0.96864 | |
Resolution limit (Å) | 92.1–3.18 (3.23–3.18) | 92.1–2.94 (3.19–2.94) |
Number of unique obs. | 22,841 (1103) | 23,054 (1153) |
Completeness (%) | 97.4 (97.0) | 91.9 (58.1) |
Multiplicity | 9.3 (5.9) | 9.2 (4.0) |
Rmerge (I) % | 0.218 (1.867) | 0.217 (1.215) |
Rpim (I) % | 0.073 (0.803) | 0.073 (0.666) |
CC1/2 | 0.995 (0.408) | 0.995 (0.361) |
I/σI | 9.0 (1.1) | 9.0 (1.4) |
Refinement | ||
Resolution range (Å) | 79.7–2.94 | |
Rcryst | 0.2470 | |
Rfree | 0.3062 | |
Number of protein atoms | 6816 | |
Number of ligand atoms | 0 | |
Number of solvent atoms | 1 | |
Mean B | 70.11 | |
Rmsd bond lengths (Å) | 0.005 | |
Rmsd bond angles (°) | 1.051 |
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Roe, S.M.; Török, Z.; McGown, A.; Horváth, I.; Spencer, J.; Pázmány, T.; Vigh, L.; Prodromou, C. The Crystal Structure of the Hsp90-LA1011 Complex and the Mechanism by Which LA1011 May Improve the Prognosis of Alzheimer’s Disease. Biomolecules 2023, 13, 1051. https://doi.org/10.3390/biom13071051
Roe SM, Török Z, McGown A, Horváth I, Spencer J, Pázmány T, Vigh L, Prodromou C. The Crystal Structure of the Hsp90-LA1011 Complex and the Mechanism by Which LA1011 May Improve the Prognosis of Alzheimer’s Disease. Biomolecules. 2023; 13(7):1051. https://doi.org/10.3390/biom13071051
Chicago/Turabian StyleRoe, S. Mark, Zsolt Török, Andrew McGown, Ibolya Horváth, John Spencer, Tamás Pázmány, László Vigh, and Chrisostomos Prodromou. 2023. "The Crystal Structure of the Hsp90-LA1011 Complex and the Mechanism by Which LA1011 May Improve the Prognosis of Alzheimer’s Disease" Biomolecules 13, no. 7: 1051. https://doi.org/10.3390/biom13071051