Inhibitory effect of boldine on TERT: In Silico study

سال انتشار: 1395
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 479

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تاریخ نمایه سازی: 7 اسفند 1396

چکیده مقاله:

Telomerase has an essential RNA and a protein reverse transcriptase subunit. The telomerase maintainstelomere length stability in almost all cancer cells that cause to their immortality. Humantelomeres(hTERT) contain long stretches of the repetitive sequence TTAGGG which are bound byspecific proteins. Cancer cells stabilize telomer length by adding TTAGGG repeats onto the telomers.Telomerase activity has been found in almost all human tumors but not in adjacent normal cells. Naturalalkaloids potentially are able to inhibit telomerase. Boldine is a natural alkaloid that is found inabundance in the leaves and bark of Peumusboldus. It is an aporphine alkaloid showed an interesting doseand time dependent anti-proliferative effect in several cancer cell lines. In this study, binding mode ofboldine-telomerase and their interactions was investigated in detail using in silico methods. There is noexperimentally 3D-structure of human telomerase (hTERT). A 3D-strucutre model for human telomerasewas constructed. Autodock software was used to study inhibitory binding mode telomerase-Boldine.Based on results, boldine inhibit telomerase with Ki: and binding energy: . Amino acids of activesite of telomerasecontaines of 343 Asp, 344 Asp, 251 Asp, lys372, Asn369, Ala 255. Boldine sit ontelomerase active site and formed three H-bonds to lys372and Asn369 andAla 255 in telomerase activesite.

کلیدواژه ها:


Fatemeh Masoumi

Department Basic Science,HakimSabzevari University, Sabzevar, Iran

Sakine Kazemi Noureini

Department Basic Science,HakimSabzevari University, Sabzevar, Iran

Mitra Kheirabadi

Department Basic Science,HakimSabzevari University, Sabzevar, Iran