Enterococcus faecalis is a gram-positive, rod-shape bacteria responsible for around 65% to 80% of all enterococcal nosocomial infections. It is multidrug resistant (MDR) bacterium resistant to most of the first-line antibiotics. Due to the emergence of MDR strains, there is an urgent need to find novel targets to develop new antibacterial drugs against E. faecalis. In this regard, we have identified naphthoate synthase (1,4-dihydroxy-2-naphthoyl-CoA synthase, EC: 4.1.3.36; DHNS) as an anti-E. faecalis target, as it is an essential enzyme for menaquinone (vitamin K2 ) synthetic pathway in the bacterium. Thus, inhibiting naphtholate synthase may consequently inhibit the bacteria's growth. In this regard, we report here cloning, expression, purification, and preliminary structural studies of naphthoate synthase along with in silico modeling, molecular dynamic simulation of the model and docking studies of naphthoate synthase with quercetin, a plant alkaloid. Biochemical studies have indicated quercetin, a plant flavonoid as the potential lead compound to inhibit catalytic activity of EfDHNS. Quercetin binding has also been validated by spectrofluorimetric studies in order to confirm the bindings of the ligand compound with EfDHNS at ultralow concentrations. Reported studies may provide a base for structure-based drug development of antimicrobial compounds against E. faecalis.

中文翻译：

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槲皮素作为粪肠球菌中萘甲酸酯合酶的潜在抑制剂的鉴定和评估。

粪肠球菌是革兰氏阳性的杆状细菌，约占所有肠球菌医院感染的65％至80％。它对大多数一线抗生素具有多重耐药性（MDR）细菌。由于MDR菌株的出现，迫切需要寻找新的靶标来开发针对粪肠球菌的新型抗菌药物。在这方面，我们已经确定了萘甲酸酯合酶（1,4-二羟基-2-萘甲酰辅酶A合酶，EC：4.1.3.36； DHNS）是抗E抗体。粪便靶标，因为它是细菌中甲萘醌（维生素K2）合成途径的必需酶。因此，抑制萘甲酸酯合酶可因此抑制细菌的生长。在这方面，我们在这里报告萘甲酸酯合酶的克隆，表达，纯化和初步结构研究，以及计算机模拟，模型的分子动力学模拟以及萘酚合酶与槲皮素（一种植物生物碱）的对接研究。生化研究表明，槲皮素是一种植物类黄酮，可能抑制EfDHNS的催化活性。槲皮素的结合也已通过荧光光谱法研究证实，以证实配体化合物与EfDHNS在超低浓度下的结合。报道的研究可能为针对粪肠球菌的抗菌化合物的基于结构的药物开发提供基础。槲皮素的结合也已通过荧光光谱法研究证实，以证实配体化合物与EfDHNS在超低浓度下的结合。报道的研究可能为针对粪肠球菌的抗菌化合物的基于结构的药物开发提供基础。槲皮素的结合也已通过荧光光谱法研究证实，以证实配体化合物与EfDHNS在超低浓度下的结合。报道的研究可能为针对粪肠球菌的抗菌化合物的基于结构的药物开发提供基础。