Identification of the Protein Binding Region ofS-Trityl-l-cysteine, a New Potent Inhibitor of the Mitotic Kinesin Eg5†

Biochemistry ◽  
2004 ◽  
Vol 43 (41) ◽  
pp. 13072-13082 ◽  
Author(s):  
Sébastien Brier ◽  
David Lemaire ◽  
Salvatore DeBonis ◽  
Eric Forest ◽  
Frank Kozielski
Keyword(s):  
Protein Binding ◽  
Potent Inhibitor ◽  
Binding Region ◽  
Protein Binding Region ◽  
Kinesin Eg5 ◽  
Mitotic Kinesin Eg5

scholarly journals Novel Photochromic Potent Inhibitor of Mitotic Kinesin Eg5 Composed of Spiropyran Derivatives

2018 ◽  
Vol 114 (3) ◽  
pp. 511a
Author(s):  
Kei Sadakane ◽  
Kenichi Taii ◽  
Shinsaku Maruta
Keyword(s):  
Potent Inhibitor ◽  
Kinesin Eg5 ◽  
Mitotic Kinesin Eg5

scholarly journals Potential involvement of monoamine oxidase activity in SARS-COV2 infection and delirium onset

2020 ◽  
Author(s):  
Miroslava Cuperlovic-Culf ◽  
Emma L. Cunningham ◽  
Anu Surendra ◽  
Xiaobei Pan ◽  
Steffany A.L. Bennett ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Monoamine Oxidase ◽  
Protein Binding ◽  
Signs And Symptoms ◽  
Spike Protein ◽  
Monoamine Oxidase B ◽  
Binding Region ◽  
Acute Confusional State ◽  
Protein Binding Region ◽  
Respiratory Signs And Symptoms

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of extra-respiratory signs and symptoms. One such manifestation is delirium, an acute confusional state occurring in 60-70% of severe SARS-CoV-2 cases. Delirium is also a common clinical syndrome following planned orthopedic surgery. This investigation initially explored the underlying role of metabolism in delirium-susceptibility in this setting. Metabolomics profiles of cerebrospinal fluid (CSF) and blood taken prior to surgery found significant concentration differences of several amino acids, acylcarnitines and polyamines were observed in delirium-prone patients. Phenethylamine (PEA) concentrations in delirium-prone patients was significantly lower in CSF than in blood, whilst in age- and gender-matched controls the opposite was observed (adjusted p values: 1.8×10−6 (control) and 1.788×10−10 (delirium)). PEA is metabolised by monoamine oxidase B (MAOB), a putative enzyme target for the treatment of Alzheimer’s disease, Parkinson’s disease and depression. Our computational structural comparisons of MAOB and angiotensin converting enzyme (ACE) 2 found high similarity, specifically within the SARS-CoV-2 spike protein. MAOB structural alignment to ACE2 was 51% overall, but this was over 95% in the ACE2-spike protein binding region. Thus, it is possible that the spike protein interacts with MAOB on a molecular level. A previously published metabolomic dataset of control subjects and patients with either mild or severe COVID-19 was then analysed. Major concentration differences in some metabolites attributed to altered MAO activity were detected. Therefore, our hypothesis is that the SARS-CoV-2 influences MAOB activity, which is one potential cause for the many observed neurological and platelet based complications of SARS-CoV-2 infection. Further research is required to establish what effect MAOB inhibitors might have on these pathways. There is no evidence at present to support the withholding of MAOB inhibitors.Significance StatementSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of extra-respiratory signs and symptoms including delirium, anosmia, intravascular coagulation. Analysis of metabolomics differences in delirium-prone patients and in severe cases of SARS-CoV2 infection indicate possibly significant role for monoamine oxidase B (MAOB). Changes in activity of MAOB have been shown in other conditions to cause range of symptoms observed in SARS-CoV2 infection. Computational structural analysis presented here demonstrations significant similarity between MAOB and ACE2 protein binding region leading to a hypothesis that SARS-CoV-2 spike protein affects MAOB activity during the infection. This proposition is possibly of significance for both diagnosis of high-risk subjects prior to infection as well as novel avenues for the development of treatment and prevention.

scholarly journals Identification of a Novel TATA Element-binding Protein Binding Region at the N Terminus of theSaccharomyces cerevisiaeTAF1 Protein

2003 ◽  
Vol 278 (46) ◽  
pp. 45888-45902 ◽  
Author(s):  
Shinya Takahata ◽  
Hidei Ryu ◽  
Kazushige Ohtsuki ◽  
Koji Kasahara ◽  
Masashi Kawaichi ◽  
...  
Keyword(s):  
Protein Binding ◽  
Binding Protein ◽  
Binding Region ◽  
Tata Element ◽  
N Terminus ◽  
Element Binding Protein ◽  
Protein Binding Region

scholarly journals Monastrol Inhibition of the Mitotic Kinesin Eg5

2005 ◽  
Vol 280 (13) ◽  
pp. 12658-12667 ◽  
Author(s):  
Jared C. Cochran ◽  
Joseph E. Gatial ◽  
Tarun M. Kapoor ◽  
Susan P. Gilbert
Keyword(s):  
Kinesin Eg5 ◽  
Mitotic Kinesin Eg5
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