Millan Sabera, Satish Lakkoji, Bera Krishnendu, Konar Monidipa, Sahoo Harekrushna
Department of Chemistry, National Institute of Technology (NIT), Rourkela, Odisha, India.
Department of Chemistry, National Institute of Technology (NIT), Rourkela, Odisha, India.
J Photochem Photobiol B. 2018 Feb;179:23-31. doi: 10.1016/j.jphotobiol.2017.12.019. Epub 2017 Dec 21.
In this present work, a detailed investigation of the effect of an anticancer drug, 5-Fluorouracil (5-FU), on conformation, stability and activity of lysozyme (Lyz) was reported. The interaction between Lyz and 5-FU was reflected in terms of intrinsic fluorescence quenching and change in secondary structure of Lyz. The mode of quenching mechanism involved was evaluated by the steady-state and time-resolved fluorescence measurements. Synchronous and Circular Dichroism (CD) results revealed the conformational changes induced in Lyz upon complexation with 5-FU. Additionally, the effect of temperature and chemical denaturant on the stability of Lyz-5FU complex was carried out. As well as the activity of Lyz in the absence and presence of 5-FU were measured using Micrococcus luteus strain. To support our experimental findings, in vitro interaction between Lyz and 5-FU was done by theoretical studies. The current study will provide a better understanding on the nature of the interactions possible between proteins and drug molecules, which might create a bench mark in medical science in terms of the toxic effect or biological benefits of drug molecules on protein structure and conformation.
在本研究中，报道了对抗癌药物5-氟尿嘧啶（5-FU）对溶菌酶（Lyz）的构象、稳定性和活性影响的详细研究。Lyz与5-FU之间的相互作用通过内在荧光猝灭和Lyz二级结构的变化得以体现。通过稳态和时间分辨荧光测量评估了所涉及的猝灭机制模式。同步和圆二色性（CD）结果揭示了Lyz与5-FU络合后诱导的构象变化。此外，还研究了温度和化学变性剂对Lyz-5FU复合物稳定性的影响。同时，使用藤黄微球菌菌株测量了有无5-FU时Lyz的活性。为支持我们的实验结果，通过理论研究对Lyz与5-FU之间的体外相互作用进行了研究。当前的研究将有助于更好地理解蛋白质与药物分子之间可能存在的相互作用的本质，这可能在药物分子对蛋白质结构和构象的毒性作用或生物学益处方面为医学科学树立一个基准。
