Pedersen Anders, Karlsson Göran B, Rydström Jan
Swedish NMR Centre, University of Gothenburg, Gothenburg, Sweden.
J Bioenerg Biomembr. 2008 Oct;40(5):463-73. doi: 10.1007/s10863-008-9170-x. Epub 2008 Oct 30.
Proton-translocating transhydrogenases, reducing NADP(+) by NADH through hydride transfer, are membrane proteins utilizing the electrochemical proton gradient for NADPH generation. The enzymes have important physiological roles in the maintenance of e.g. reduced glutathione, relevant for essentially all cell types. Following X-ray crystallography and structural resolution of the soluble substrate-binding domains, mechanistic aspects of the hydride transfer are beginning to be resolved. However, the structure of the intact enzyme is unknown. Key questions regarding the coupling mechanism, i.e., the mechanism of proton translocation, are addressed using the separately expressed substrate-binding domains. Important aspects are therefore which functions and properties of mainly the soluble NADP(H)-binding domain, but also the NAD(H)-binding domain, are relevant for proton translocation, how the soluble domains communicate with the membrane domain, and the mechanism of proton translocation through the membrane domain.
质子转运型转氢酶通过氢化物转移利用NADH还原NADP(+)，是利用电化学质子梯度生成NADPH的膜蛋白。这些酶在维持例如还原型谷胱甘肽方面具有重要的生理作用，这对基本上所有细胞类型都至关重要。随着可溶性底物结合结构域的X射线晶体学和结构解析，氢化物转移的机制方面开始得到解决。然而，完整酶的结构尚不清楚。使用单独表达的底物结合结构域来解决有关偶联机制（即质子转运机制）的关键问题。因此，重要的方面是主要可溶性NADP(H)结合结构域以及NAD(H)结合结构域的哪些功能和特性与质子转运相关，可溶性结构域如何与膜结构域通信，以及质子通过膜结构域的转运机制。
