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首页> 外文期刊>Microbial Pathogenesis >Characterization of serine acetyltransferase (CysE) from methicillin-resistant Staphylococcus aureus and inhibitory effect of two natural products on CysE
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Characterization of serine acetyltransferase (CysE) from methicillin-resistant Staphylococcus aureus and inhibitory effect of two natural products on CysE

机译：来自耐甲氧西林金黄色葡萄球菌的丝氨酸乙酰转移酶（CYSE）的表征及两种天然产物对CYSE的抑制作用

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摘要

Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital-acquired infective pathogen that has developed resistance to many antibiotics. It is imperious to develop novel anti-MRSA drugs to control the emergence of drug resistance. The biosynthesis of cysteine in bacteria is catalyzed by CysE and CysK. CysE was predicted to be important for bacterial viability, it could be a potential drug target. The serine acetyltransferase activity of CysE was detected and its catalytic properties were also determined. CysE homology model was built to investigate interaction sites between CysE and substrate L-Ser or inhibitors by molecular docking. Docking data showed that residues Asp94 and His95 were essential for serine acetyltransferase activity of CysE, which were confirmed by site-directed mutagenesis. Colorimetric assay was used to screen natural products and six compounds which inhibited CysE activity (IC50 ranging from 29.83 mu M to 203.13 mu M) were found. Inhibition types of two compounds 4 (11-oxo-ebracteolatanolide B) and 30 ((4R,4aR)-dihydroxy-3-hydroxymethyl-7,7,10a-trimethyl-2,4,4a,5,6,6a,7,8,9,10,10a,10b-dodecahydrophenanthro [3,2-b]furan-2-one) on CysE were determined. Compounds 4 and 30 showed inhibitory effect on MRSA growth (MIC at 12.5 mu g/ml and 25 mu g/ml) and mature biofilm. The established colorimetric assay will facilitate further high-throughput screening of CysE inhibitors from different compound libraries. The compounds 4 and 30 may offer structural basis for developing new anti-MRSA drugs.
机译：耐甲氧西林葡萄球菌金黄色葡萄球菌（MRSA）是一种主要的医院获得的感染病原体，其对许多抗生素产生了抗性。促使新型抗MRSA药物造成新的抗MRSA药物来控制耐药性的出现。细菌中半胱氨酸的生物合成是通过Cyse和Cysk催化的。预计Cyse对于细菌活力是重要的，它可能是潜在的药物目标。检测到Cyse的丝氨酸乙酰转移酶活性，并且还测定其催化性质。通过分子对接，构建了Cyse同源模型以研究Cyse和衬底L-SER或抑制剂之间的相互作用位点。对接数据显示残留物ASP94和HIS95对于Cyse的丝氨酸乙酰转移酶活性是必不可少的，其通过定点诱变证实。比色测定用于筛选天然产物和抑制Cyse活性的六种化合物（IC50，范围为29.83μm至203.13μm）。两种化合物4（11-氧代 - 埃布拉酰替丹醇醚B）和30的抑制类型（（4R，4AR） - 羟基-3-羟甲基-7,7,10A-三甲基-2,4,4a，5,6,68,7 ，测定了8,9,10,10A，10B-十二烷糖酚酚[3,2-B]呋喃-2-一体化）。化合物4和30显示对MRSA生长的抑制作用（MIC为12.5μg/ ml和25μg/ ml）和成熟的生物膜。已建立的比色测定将促进来自不同复合文库的Cyse抑制剂的进一步高通量筛选。化合物4和30可以为开发新的抗MRSA药物提供结构依据。

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