Frank René A W, Pratap J Venkatesh, Pei Xue Y, Perham Richard N, Luisi Ben F
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
Structure. 2005 Aug;13(8):1119-30. doi: 10.1016/j.str.2005.04.021.
The pyruvate dehydrogenase (PDH) multienzyme complex is central to oxidative metabolism. We present the first crystal structure of a complex between pyruvate decarboxylase (E1) and the peripheral subunit binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2). The interface is dominated by a "charge zipper" of networked salt bridges. Remarkably, the PSBD uses essentially the same zipper to alternately recognize the dihydrolipoyl dehydrogenase (E3) component of the PDH assembly. The PSBD achieves this dual recognition largely through the addition of a network of interfacial water molecules unique to the E1-PSBD complex. These structural comparisons illuminate our observations that the formation of this water-rich E1-E2 interface is largely enthalpy driven, whereas that of the E3-PSBD complex (from which water is excluded) is entropy driven. Interfacial water molecules thus diversify surface complementarity and contribute to avidity, enthalpically. Additionally, the E1-PSBD structure provides insight into the organization and active site coupling within the approximately 9 MDa PDH complex.
丙酮酸脱氢酶（PDH）多酶复合体是氧化代谢的核心。我们展示了丙酮酸脱羧酶（E1）与二氢硫辛酰胺乙酰转移酶（E2）的外周亚基结合结构域（PSBD）之间复合物的首个晶体结构。该界面主要由相互连接的盐桥形成的“电荷拉链”主导。值得注意的是，PSBD利用基本相同的拉链交替识别PDH组装体的二氢硫辛酰胺脱氢酶（E3）组分。PSBD实现这种双重识别主要是通过添加E1-PSBD复合物特有的界面水分子网络。这些结构比较阐明了我们的观察结果，即这种富含水的E1-E2界面的形成在很大程度上是由焓驱动的，而E3-PSBD复合物（其中水被排除）的形成是由熵驱动的。因此，界面水分子使表面互补性多样化，并在焓方面有助于亲和力。此外，E1-PSBD结构为约9 MDa的PDH复合物中的组织和活性位点偶联提供了见解。
