EVIDENCE THAT THE NOVOBIOCIN-SENSITIVE ATP-BINDING SITE OF THE HEAT SHOCK PROTEIN 90 (HSP90) IS NECESSARY FOR ITS AUTOPHOSPHORYLATION

2002 ◽  
Vol 26 (7) ◽  
pp. 653-657 ◽  
Author(s):  
T Langer
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Binding Site ◽  
Heat Shock Protein 90 ◽  
Atp Binding ◽  
Atp Binding Site

scholarly journals Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics

Open Biology ◽  
2012 ◽  
Vol 2 (12) ◽  
pp. 120138 ◽  
Author(s):  
Peter W. Piper ◽  
Stefan H. Millson
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Binding Site ◽  
Cancer Progression ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Cancer Drug ◽  
Atp Binding ◽  
Hsp90 Inhibition ◽  
Atp Binding Site

Heat shock protein 90 (Hsp90) is a promising cancer drug target as a molecular chaperone critical for stabilization and activation of several of the oncoproteins that drive cancer progression. Its actions depend upon its essential ATPase, an activity fortuitously inhibited with a very high degree of selectivity by natural antibiotics: notably the actinomycete-derived benzoquinone ansamycins (e.g. geldanamycin) and certain fungal-derived resorcyclic acid lactones (e.g. radicicol). The molecular interactions made by these antibiotics when bound within the ADP/ATP-binding site of Hsp90 have served as templates for the development of several synthetic Hsp90 inhibitor drugs. Much attention now focuses on the clinical trials of these drugs. However, because microbes have evolved antibiotics to target Hsp90, it is probable that they often exploit Hsp90 inhibition when interacting with each other and with plants. Fungi known to produce Hsp90 inhibitors include mycoparasitic, as well as plant-pathogenic, endophytic and mycorrhizal species. The Hsp90 chaperone may, therefore, be a prominent target in establishing a number of mycoparasitic (interfungal), fungal pathogen–plant and symbiotic fungus–plant relationships. Furthermore the Hsp90 family proteins of the microbes that produce Hsp90 inhibitor antibiotics are able to reveal how drug resistance can arise by amino acid changes in the highly conserved ADP/ATP-binding site of Hsp90.

scholarly journals Mebendazole’s Conformational Space and its Predicted Binding to Human Heat-Shock Protein 90

2021 ◽  
Author(s):  
Walter Fiedler ◽  
Fabian Freisleben ◽  
Jasmin Wellbrock ◽  
Karl Kirschner
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Binding Site ◽  
Leukemia Cell ◽  
Heat Shock Protein 90 ◽  
Md Simulations ◽  
Conformational Space ◽  
Atp Binding ◽  
Atp Binding Site ◽  
Experimental Crystal

Recent experimental evidence suggest that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibit acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triphosphate (ATP) binding site of Hsp90. Extensive conformational searches and minimization of the five tautomers of mebendazole using MP2/aug-cc-pVTZ theory level resulting in 152 minima being identified. Mebendazole-Hsp90 complex models were created using the QM optimized conformations and protein coordinates obtained from experimental crystal structures that were chosen through similarity calculations. Nine different poses were identified from a total of 600 ns of explicit solvent, all-atom MD simulations using two different force fields. All simulations support the hypothesis that mebendazole is able to bind to the ATP binding site of Hsp90.

scholarly journals The Heat Shock Protein 90 Antagonist Novobiocin Interacts with a Previously Unrecognized ATP-binding Domain in the Carboxyl Terminus of the Chaperone

2000 ◽  
Vol 275 (47) ◽  
pp. 37181-37186 ◽  
Author(s):  
Monica G. Marcu ◽  
Ahmed Chadli ◽  
Ilham Bouhouche ◽  
Maria Catelli ◽  
Leonard M. Neckers
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Binding Domain ◽  
Carboxyl Terminus ◽  
Atp Binding

Balancing selection at the ATP binding site of heat shock cognate 70 (HSC70) contributes to increased thermotolerance in Artemia franciscana

Aquaculture ◽  
2021 ◽  
Vol 531 ◽  
pp. 735988
Author(s):  
Wisarut Junprung ◽  
Premruethai Supungul ◽  
Anchalee Tassanakajon ◽  
Gilbert Van Stappen ◽  
Peter Bossier
Keyword(s):  
Heat Shock ◽  
Binding Site ◽  
Balancing Selection ◽  
Artemia Franciscana ◽  
Atp Binding ◽  
Atp Binding Site ◽  
Heat Shock Cognate 70

Synthesis and Evaluation of a Novel Deguelin Derivative, L80, which Disrupts ATP Binding to the C-terminal Domain of Heat Shock Protein 90

2015 ◽  
Vol 88 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Su-Chan Lee ◽  
Hye-Young Min ◽  
Hoon Choi ◽  
Ho Shin Kim ◽  
Kyong-Cheol Kim ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Atp Binding ◽  
Terminal Domain
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