Division of Biochemistry and Molecular Biology, Louisiana State University, Baton Rouge, LA 70803, USA.
Structure. 2013 Apr 2;21(4):650-7. doi: 10.1016/j.str.2013.02.001. Epub 2013 Mar 14.
Acetyl-coenzyme A (acetyl-CoA) carboxylase is a biotin-dependent, multifunctional enzyme that catalyzes the regulated step in fatty acid synthesis. The Escherichia coli enzyme is composed of a homodimeric biotin carboxylase (BC), biotinylated biotin carboxyl carrier protein (BCCP), and an α2β2 heterotetrameric carboxyltransferase. This enzyme complex catalyzes two half-reactions to form malonyl-coenzyme A. BC and BCCP participate in the first half-reaction, whereas carboxyltransferase and BCCP are involved in the second. Three-dimensional structures have been reported for the individual subunits; however, the structural basis for how BCCP reacts with the carboxylase or transferase is unknown. Therefore, we report here the crystal structure of E. coli BCCP complexed with BC to a resolution of 2.49 Å. The protein-protein complex shows a unique quaternary structure and two distinct interfaces for each BCCP monomer. These BCCP binding sites are unique compared to phylogenetically related biotin-dependent carboxylases and therefore provide novel targets for developing antibiotics against bacterial acetyl-CoA carboxylase.
乙酰辅酶 A（acetyl-CoA）羧化酶是一种生物素依赖性的多功能酶，催化脂肪酸合成的调节步骤。大肠杆菌中的酶由一个同二聚体生物素羧化酶（BC）、生物素化的生物素羧基载体蛋白（BCCP）和一个 α2β2 异四聚体羧基转移酶组成。该酶复合物催化两个半反应形成丙二酰辅酶 A。BC 和 BCCP 参与第一个半反应，而羧基转移酶和 BCCP 参与第二个半反应。已经报道了各个亚基的三维结构；然而，BCCP 与羧化酶或转移酶反应的结构基础尚不清楚。因此，我们在此报告了大肠杆菌 BCCP 与 BC 复合物的晶体结构，分辨率为 2.49Å。该蛋白-蛋白复合物显示出独特的四级结构和每个 BCCP 单体的两个不同界面。与系统发育上相关的生物素依赖性羧化酶相比，这些 BCCP 结合位点是独特的，因此为开发针对细菌乙酰辅酶 A 羧化酶的抗生素提供了新的靶点。
