论文标题
TTGR调节剂和效应子的量子生化分析
Quantum Biochemical Analysis of the TtgR Regulator and Effectors
论文作者
论文摘要
最近的抗多药（MDR）病原体的扩张在治疗医疗保健相关感染方面面临着重大挑战。尽管抗菌抗性是通过多种机制发生的，但药物的主动排出是一个关键问题。单一物种的外排泵可以同时对几种药物产生抗性。 ttgaBC是最久经考验的外排泵之一：三方耐药性 - 结构分割（RND）外排泵，该泵与假单胞菌putida dot-t1e中的固有抗生素耐药性有关。 TTGABC基因的表达被HTH型转录阻遏物TTGR下调。 In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two广谱抗菌剂。我们的量子生化计算结果表明：[I]收敛半径，[ii]配体区域的总结合能，[iii]相关性（iii]相关性，以及[iv] [iv]最相关的氨基酸残基，ttgr-que/tac/clm络合物中的最相关性和相似之处。这些发现提高了对效应子的结合机制的理解，并促进了针对TTGR的新化学物质的发展，有助于与抗菌药物抗性的抗击作斗争。
The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs.
