a National Institute of Chemistry , Ljubljana , Slovenia.
b Department of Biochemistry, Molecular and Structural Biology , Jozef Stefan Institute , Ljubljana , Slovenia.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):1239-1247. doi: 10.1080/14756366.2018.1493474.
Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target.
自溶素 E（AtlE）是一种细胞壁降解酶，可催化 N-乙酰葡萄糖胺和 N-乙酰胞壁酸单元之间的β-1,4-糖苷键的水解。利用我们最近从金黄色葡萄球菌确定的 AtlE 晶体结构，结合药效团建模、相似性搜索和分子对接，鉴定出一系列（苯并脒基）哌啶基苯甲酰胺作为潜在的结合物，表面等离子体共振（SPR）和饱和转移差异（STD）NMR 实验表明，发现的化合物以低微摩尔范围与 AtlE 结合。（苯并脒基）哌啶基苯甲酰胺是首次报道的与该酶相互作用的非底物样化合物，并能够进一步研究小分子与细菌 AtlE 的相互作用，作为该靶标的潜在抑制剂。
