Structure, Substrate Recognition, and Mechanism of the Na+-Hydantoin Membrane Transport Protein, Mhp1
Structure, Substrate Recognition, and Mechanism of the Na+-Hydantoin Membrane Transport Protein, Mhp1
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Na-乙内酰脲膜转运蛋白 Mhp1 的结构、底物识别和机制
DOI：
10.1007/978-3-642-35943-9_10091-1
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发表时间：
2018
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et al.
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作者：
Jackson Scott M.、Ivanova Ekaterina、Calabrese Antonio N.、Polyakova Anna、Sharples David J.、Shimamura Tatsuro、Cameron Alexander D.、Henderson Peter J. F.;et al.
NCS-1家族中第一个确定其结构的蛋白质Mhp1，出人意料地被证明在蛋白质折叠上与神经递质钠转运体(NSS)家族的Leut蛋白质相似(Yamashita等人)。2005)和vSGLT糖钠转运体(SSS)家族(Faham等.2008)，最初根据它们的氨基酸序列的不同而被归类为无关(Saier等人。2006)。因此，NCS-1家族是后来扩展的转运蛋白超家族的一部分，该家族被称为氨基酸-多胺有机化(APC)超家族(Vastermak等人)。2014)，Leut超家族，或五螺旋反向重复转运蛋白(5HIRT)超家族(Adelman等人。2011年)。Mhp1的结构现在已经被确定为四种构象，包括开放、底物封闭、抑制剂封闭和开放，以及分子动力学模拟预测的另一种形式，这阐明了交替访问机制的结构和分子基础(Weyand等人)。2008、2011；Shimamura et al.2010)。纯化的Mhp1蛋白对于包括结晶在内的一系列生物物理和生化技术来说是足够稳定的(Shimamura等人。2008)、X射线衍射(Weyand等人)。2008年；Shimamura et al.2010年；西蒙斯等人。2014)、化学修饰(Calabrese等人2017年；Majd等人，未公布的数据)，质谱学(Calabrese等人。2017)，分光光度荧光法(Weyand等人2008)和电子顺磁共振(Kazmier等人)。2014年)。此外，它的构象变化的动力学已经在分子模拟中被模拟(例如，Shimamura等人。2010年；Adelman等人。2011年；宋朱2015年；萨海，未出版)。
The first protein of the NCS-1 family to have its structure determined, Mhp1, unexpectedly turned out to be similar in protein fold to the LeuT protein from the neurotransmitter sodium symporter (NSS) family (Yamashita et al. 2005) and the vSGLT sugar sodium symporter (SSS) family (Faham et al. 2008), originally classified as unrelated according to the dissimilarities of their amino acid sequences (Saier et al. 2006). The NCS-1 family is, therefore, part of a subsequently much extended transporter superfamily that has been termed the amino acid-polyamineorganocation (APC) superfamily (Vastermak et al. 2014), the LeuT superfamily, or the five-helix inverted repeat transporter (5HIRT) superfamily (Adelman et al. 2011). The structure of Mhp1 has now been determined in four conformations, including open out, occluded with substrate, occluded with inhibitor, and open in, together with an additional form predicted by molecular dynamics simulations, which illuminate the structural and molecular basis of the alternating access mechanism (Weyand et al. 2008, 2011; Shimamura et al. 2010). The purified Mhp1 protein is sufficiently stable for a range of biophysical and biochemical techniques including crystallization (Shimamura et al. 2008), X-ray diffraction (Weyand et al. 2008; Shimamura et al. 2010; Simmons et al. 2014), chemical modification (Calabrese et al. 2017; Majd et al., unpublished data), mass spectrometry (Calabrese et al. 2017), spectrophotofluorimetry (Weyand et al. 2008), and electron paramagnetic resonance (Kazmier et al. 2014). Additionally, the dynamics of its changes in conformation have been modeled in molecular simulations (eg, Shimamura et al. 2010; Adelman et al. 2011; Song and Zhu 2015; Sahai, unpublished).