Gushchina I V, Nilov D K, Shcherbakova T A, Baldin S M, Švedas V K
Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119234 Russian Federation.
Lomonosov Moscow State University, Belozersky Institute of Physicochemical Biology, Moscow, 119234 Russian Federation.
Acta Naturae. 2023 Apr-Jun;15(2):81-83. doi: 10.32607/actanaturae.15709.
As a result of the computer screening of a library of sulfo-substituted compounds, molecules capable of binding to the active site of transketolase from were identified. An experimental verification of the inhibitory activity of the most promising compound, STK045765, against a highly purified recombinant enzyme preparation was carried out. It was shown that the STK045765 molecule competes for the binding site of the pyrophosphate group of the thiamine diphosphate cofactor and, at a micromolar concentrations, is able to suppress the activity of mycobacterial transketolase. The discovered furansulfonate scaffold may serve as the basis for the creation of anti-tuberculosis drugs.
通过对磺基取代化合物文库进行计算机筛选，鉴定出了能够与来自[具体来源未给出]的转酮醇酶活性位点结合的分子。对最有前景的化合物STK045765针对高度纯化的重组酶制剂的抑制活性进行了实验验证。结果表明，STK045765分子竞争硫胺二磷酸辅因子焦磷酸基团的结合位点，并且在微摩尔浓度下能够抑制分枝杆菌转酮醇酶的活性。所发现的呋喃磺酸盐支架可作为开发抗结核药物的基础。
