School of Chemistry, National University of Ireland, Galway, Ireland.
Proteins. 2011 May;79(5):1564-72. doi: 10.1002/prot.22983. Epub 2011 Mar 4.
Listeria monocytogenes is one of the most virulent foodborne pathogens. L. monocytogenes Sortase A (SrtA) enzyme, which catalyzes the cell wall anchoring reaction of the leucine, proline, X, threonine, and glycine proteins (LPXTG, where X is any amino acid), is a target for the development of antilisteriosis drugs. In this study, the structure of the L. monocytogenes SrtA enzyme-substrate complex was obtained using homology modeling, molecular docking and molecular dynamics simulations. Explicit enzyme-substrate interactions in the inactive and active forms of the enzyme were compared, based on 30 ns simulations on each system. The active site arginine (Arg 197) was found to be able change its hydrogen donor interactions from the LP backbone carbonyl groups of the LPXTG substrate in the inactive form, to the TG backbone carbonyls in the active form, which could be of importance for holding the substrate in position for the catalytic process.
李斯特菌是最致命的食源性病原体之一。李斯特菌 SrtA 酶（Sortase A）可催化亮氨酸-脯氨酸-X-苏氨酸-甘氨酸蛋白（LPXTG，其中 X 是任何氨基酸）的细胞壁锚定反应，是开发抗李斯特菌药物的靶点。在这项研究中，使用同源建模、分子对接和分子动力学模拟获得了李斯特菌 SrtA 酶-底物复合物的结构。基于每个系统 30ns 的模拟，比较了酶的无活性和有活性形式下的酶-底物的明确相互作用。发现活性部位的精氨酸（Arg197）能够将其氢键供体相互作用从无活性形式的 LPXTG 底物的 LP 主链羰基改变为活性形式的 TG 主链羰基，这对于将底物保持在催化过程的位置可能很重要。
