scholarly journals Identification of a Hydrophobic Cleft in the LytTR Domain of AgrA as a Locus for Small Molecule Interactions That Inhibit DNA Binding

Biochemistry ◽  
2012 ◽  
Vol 51 (50) ◽  
pp. 10035-10043 ◽  
Author(s):  
Paul G. Leonard ◽  
Ian F. Bezar ◽  
David J. Sidote ◽  
Ann M. Stock
Keyword(s):  
Dna Binding ◽  
Small Molecule ◽  
Molecule Interactions ◽  
Hydrophobic Cleft

Small Molecule Interactions with Protein−Tyrosine Phosphatase PTP1B and Their Use in Inhibitor Design†

Biochemistry ◽  
1996 ◽  
Vol 35 (50) ◽  
pp. 15989-15996 ◽  
Author(s):  
Terrence R. Burke, ◽  
Bin Ye ◽  
Xinjian Yan ◽  
Shaomeng Wang ◽  
Zongchao Jia ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Inhibitor Design ◽  
Protein Tyrosine ◽  
Molecule Interactions

scholarly journals Quantifying the Selectivity of Protein–Protein and Small Molecule Interactions with Fluorinated Tandem Bromodomain Reader Proteins

2020 ◽  
Vol 15 (11) ◽  
pp. 3038-3049
Author(s):  
Prakriti Kalra ◽  
Logan McGraw ◽  
Jennifer R. Kimbrough ◽  
Anil K. Pandey ◽  
Jonathan Solberg ◽  
...  
Keyword(s):  
Small Molecule ◽  
Molecule Interactions

scholarly journals Screening antiproliferative drug for breast cancer from bisbenzylisoquinoline alkaloid tetrandrine and fangchinoline derivatives by targeting BLM helicase

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wangming Zhang ◽  
Shuang Yang ◽  
Jinhe Liu ◽  
Linchun Bao ◽  
He Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Binding ◽  
Small Molecules ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Dna Unwinding ◽  
Protein Levels ◽  
Blm Helicase ◽  
Bisbenzylisoquinoline Alkaloids

Abstract Background The high expression of BLM (Bloom syndrome) helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to screen potential antiproliferative small molecules from 12 small molecules (the derivatives of bisbenzylisoquinoline alkaloids tetrandrine and fangchinoline) by targeting BLM642–1290 helicase. Then we explore the inhibitory mechanism of those small molecules on proliferation of MDA-MB-435 breast cancer cells. Methods Fluorescence polarization technique was used to screen small molecules which inhibited the DNA binding and unwinding of BLM642–1290 helicase. The effects of positive small molecules on the ATPase and conformation of BLM642–1290 helicase were studied by the malachite green-phosphate ammonium molybdate colorimetry and ultraviolet spectral scanning, respectively. The effects of positive small molecules on growth of MDA-MB-435 cells were studied by MTT method, colony formation and cell counting method. The mRNA and protein levels of BLM helicase in the MDA-MB-435 cells after positive small molecule treatments were examined by RT-PCR and ELISA, respectively. Results The compound HJNO (a tetrandrine derivative) was screened out which inhibited the DNA binding, unwinding and ATPase of BLM642–1290 helicase. That HJNO could bind BLM642–1290helicase to change its conformationcontribute to inhibiting the DNA binding, ATPase and DNA unwinding of BLM642–1290 helicase. In addition, HJNO showed its inhibiting the growth of MDA-MB-435 cells. The values of IC50 after drug treatments for 24 h, 48 h and 72 h were 19.9 μmol/L, 4.1 μmol/L and 10.9 μmol/L, respectively. The mRNA and protein levels of BLM helicase in MDA-MB-435 cells increased after HJNO treatment. Those showed a significant difference (P < 0.05) compared with negative control when the concentrations of HJNO were 5 μmol/L and 10 μmol/L, which might contribute to HJNO inhibiting the DNA binding, ATPase and DNA unwinding of BLM helicase. Conclusion The small molecule HJNO was screened out by targeting BLM642–1290 helicase. And it showed an inhibition on MDA-MB-435 breast cancer cells expansion.

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