Peuckert Florian, Ramos-Vega Ana Laura, Miethke Marcus, Schwörer Clemens J, Albrecht Alexander G, Oberthür Markus, Marahiel Mohamed A
Department of Chemistry, Biochemistry, Philipps-University Marburg, Hans-Meerwein-Straße, D-35032 Marburg, Germany.
Chem Biol. 2011 Jul 29;18(7):907-19. doi: 10.1016/j.chembiol.2011.05.006.
Iron acquisition by siderophores is crucial for survival and virulence of many microorganisms. Here, we investigated the binding of the exogenous siderophore ferric enterobactin and the synthetic siderophore mimic ferric mecam by the triscatecholate binding protein FeuA from Bacillus subtilis at the atomic level. The structural complexes provide molecular insights into the capture mechanism of FeuA for exogenous and synthetic siderophores. The protein-ligand complexes show an exclusive acceptance of Λ-stereoconfigured substrates. Ligand-induced cross-bridging of the complexes was not observed, revealing a different thermodynamic behavior especially of the ferric mecam substrate, which was previously shown to dimerize with the enterobactin binding protein CeuE. The nearly identical overall domain movement of FeuA upon binding of ferric enterobactin or ferric mecam compared with endogenously derived ferric bacillibactin implies the importance of the conserved domain rearrangement for recognition by the transmembrane permease FeuBC, for which the conserved FeuA residues E90 and E221 were proved to be essential.
通过铁载体获取铁对于许多微生物的生存和毒力至关重要。在此，我们在原子水平上研究了外源铁载体肠杆菌素铁和合成铁载体类似物美卡霉素铁与枯草芽孢杆菌的三聚儿茶酚结合蛋白FeuA的结合情况。这些结构复合物为FeuA对外源和合成铁载体的捕获机制提供了分子层面的见解。蛋白质 - 配体复合物表现出对Λ - 立体构型底物的专一性接纳。未观察到复合物的配体诱导交叉桥连，这揭示了特别是美卡霉素铁底物的不同热力学行为，该底物先前已被证明可与肠杆菌素结合蛋白CeuE二聚化。与内源性来源的芽孢杆菌铁载体铁结合时相比，FeuA在结合肠杆菌素铁或美卡霉素铁时几乎相同的整体结构域运动意味着保守的结构域重排对于跨膜通透酶FeuBC识别的重要性，已证明保守的FeuA残基E90和E221对此至关重要。
