دورية أكاديمية
Interaction of the mitotic inhibitor monastrol with human kinesin Eg5.
| العنوان: | Interaction of the mitotic inhibitor monastrol with human kinesin Eg5. |
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| المؤلفون: | Salvatore DeBonis, Jean-Pierre Simorre, Isabelle Crevel, Luc Lebeau, Dimitrios A Skoufias, Anne Blangy, Christine Ebel, Pierre Gans, Robert Cross, David Hackney, Richard H Wade, Frank Kozielski |
| سنة النشر: | 2018 |
| المجموعة: | KiltHub Research from Carnegie Mellon University |
| مصطلحات موضوعية: | Biological Sciences not elsewhere classified, Adenosine Diphosphate, Adenosine Triphosphate, Animals, Cattle, Dose-Response Relationship, Drug, Dyneins, Enzyme Activation, Growth Inhibitors, HeLa Cells, Humans, Inhibitory Concentration 50, Kinesin, Microscopy, Interference, Video, Microtubules, Nuclear Magnetic Resonance, Biomolecular, Peptide Fragments, Protein Structure, Tertiary, Pyrimidines, Sequence Deletion, Sodium Chloride, Stereoisomerism, Thiones, ortho-Aminobenzoates |
| الوصف: | The microtubule-dependent kinesin-like protein Eg5 from Homo sapiens is involved in the assembly of the mitotic spindle. It shows a three-domain structure with an N-terminal motor domain, a central coiled coil, and a C-terminal tail domain. In vivo HsEg5 is reversibly inhibited by monastrol, a small cell-permeable molecule that causes cells to be arrested in mitosis. Both monomeric and dimeric Eg5 constructs have been examined in order to define the minimal monastrol binding domain on HsEg5. NMR relaxation experiments show that monastrol interacts with all of the Eg5 constructs used in this study. Enzymatic techniques indicate that monastrol partially inhibits Eg5 ATPase activity by binding directly to the motor domain. The binding is noncompetitive with respect to microtubules, indicating that monastrol does not interfere with the formation of the motor-MT complex. The binding is not competitive with respect to ATP. Both enzymology and in vivo assays show that the S enantiomer of monastrol is more active than the R enantiomer and racemic monastrol. Stopped-flow fluorometry indicates that monastrol inhibits ADP release by forming an Eg5-ADP-monastrol ternary complex. Monastrol reversibly inhibits the motility of human Eg5. Monastrol has no inhibitory effect on the following members of the kinesin superfamily: MC5 (Drosophila melanogaster Ncd), HK379 (H. sapiens conventional kinesin), DKH392 (D. melanogaster conventional kinesin), BimC1-428 (Aspergillus nidulans BimC), Klp15 (Caenorhabditis elegans C-terminal motor), or Nkin460GST (Neurospora crassa conventional kinesin). |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/Interaction_of_the_mitotic_inhibitor_monastrol_with_human_kinesin_Eg5_/6099713Test |
| DOI: | 10.1184/r1/6099713.v1 |
| الإتاحة: | https://doi.org/10.1184/r1/6099713.v1Test https://figshare.com/articles/Interaction_of_the_mitotic_inhibitor_monastrol_with_human_kinesin_Eg5_/6099713Test |
| حقوق: | In Copyright |
| رقم الانضمام: | edsbas.EA90A4F2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1184/r1/6099713.v1 |
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