Proton-Translocating Nicotinamide Nucleotide Transhydrogenase: A Structural Perspective.

Proton-Translocating Nicotinamide Nucleotide Transhydrogenase: A Structural Perspective.
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DOI:
10.3389/fphys.2017.01089
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发表时间:
2017
影响因子:
4
通讯作者:
Leung JH
Leung JH
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Q;Padayatti PS;Leung JH

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烟酰胺核苷酸转氢酶(TH)是动物线粒体和细菌中的酶复合物,其利用跨膜的电化学质子梯度来驱动NADPH的产生。这种酶在维持细胞的氧化还原平衡方面起着重要作用,与衰老和许多人类疾病有关。TH以同源二聚体形式存在,每个原聚体含有质子转运跨膜结构域和两个可溶性核苷酸结合结构域,其介导NAD(H)和NADP(H)之间的氢化物转移。TH的三结构域结构在物种间是保守的,但多肽组成差异很大。TH的复杂结构域偶联机制尚未完全理解,尽管广泛的生化和结构表征。本文综述了近年来嗜热栖热菌可溶性结构域和跨膜结构域的三维结晶结构研究进展。一个结构的角度和阻碍进一步阐明TH的机制的挑战进行了讨论。
Nicotinamide nucleotide transhydrogenase (TH) is an enzyme complex in animal mitochondria and bacteria that utilizes the electrochemical proton gradient across membranes to drive the production of NADPH. The enzyme plays an important role in maintaining the redox balance of cells with implications in aging and a number of human diseases. TH exists as a homodimer with each protomer containing a proton-translocating transmembrane domain and two soluble nucleotide binding domains that mediate hydride transfer between NAD(H) and NADP(H). The three-domain architecture of TH is conserved across species but polypeptide composition differs substantially. The complex domain coupling mechanism of TH is not fully understood despite extensive biochemical and structural characterizations. Herein the progress is reviewed, focusing mainly on structural findings from 3D crystallization of isolated soluble domains and more recently of the transmembrane domain and the holo-enzyme from Thermus thermophilus. A structural perspective and impeding challenges in further elucidating the mechanism of TH are discussed.
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