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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Modification of drug-binding proteins associated with the efflux pump in MDR-MTB in course of evolution: an unraveled clue based on in silico approach
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Modification of drug-binding proteins associated with the efflux pump in MDR-MTB in course of evolution: an unraveled clue based on in silico approach

机译：在演化过程中改变与MDR-MTB中的泵浦泵相关的药物结合蛋白：基于硅方法的解开线索

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Mycobacterium tuberculosis (MTB) is commonly resistant to various drugs. Multidrug-resistant tuberculosis (MDR-MTB) is mostly caused by mutation in drug-binding proteins and protein folding. The aim of the study was to identify the pattern of mutations in embC, inhA and rpoB proteins and investigate its interactions with available drug such as rifampicin, ethambutol and isoniazid, using a computer docking method. The evolution of drugs resistant mechanisms of MTB was analyzed using an in silico approach. The model proteins were considered to be in a protein-protein interaction network among the twenty transmembrane proteins. The changes in structural conformation may describe the significance of the proton pumps system. The docking analysis revealed that unlike isoniazid, both rifampicin and ethambutol, bound to the same residues in mutant and wild forms. Moreover, multiple-sequence alignment (MSA) showed mutational hotspot regions where the substitution of amino acids in these three target proteins was position specific under stress. The molecular basis of drug resistance in M. tuberculosis can be represented by a protein network which is a well-regulated system for efflux pump activation by popularly used drugs. Ethambutol and rifampicin form stable complexes with EmbC and RpoB, respectively. Isoniazid shows no binding affinity to mutant InhA (2015). Analysis of the cellular network associated with drug regulatory proteins suggest that mmp13, Rv1634 and Rv1258c play a major role by altering the protein pump to remove the active drug compounds from the bacterial cell.
机译：结核分枝杆菌（MTB）通常对各种药物耐药。多药结核（MDR-MTB）主要由药物结合蛋白和蛋白质折叠中的突变引起。该研究的目的是使用计算机对接方法鉴定emc，Inha和RPOB蛋白中的突变模式，并研究其与利福平，乙胺醇和异烟肼等可用药物的相互作用。用硅方法分析了MTB的药物抗性机制的演变。模型蛋白被认为是20个跨膜蛋白中的蛋白质 - 蛋白质相互作用网络中。结构构象的变化可以描述质子泵系统的重要性。对接分析表明，与异南菌素和乙胺醇不同，与突变和野生形式的相同残留物不同。此外，多序列对准（MSA）显示了突变热点区域，其中在这三种靶蛋白中取代氨基酸是在应激下的特异性位置。结核病耐药性的分子基础可通过蛋白质网络代表，该蛋白质网络是通过普遍使用的药物进行抑制泵激活的调节系统。乙胺丁醇和利福平分别与eMC和RPOB分别形成稳定的复合物。 Isoniazid显示对突变体Inha（2015）没有结合亲和力。与药物调节蛋白相关的细胞网络的分析表明，MMP13，RV1634和RV1258C通过改变蛋白质泵从细菌细胞中除去活性药物化合物的主要作用。

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