Cryo-EM density map fitting driven in-silico structure of human soluble guanylate cyclase (hsGC) reveals functional aspects of inter-domain cross talk upon NO binding.
Cryo-EM density map fitting driven in-silico structure of human soluble guanylate cyclase (hsGC) reveals functional aspects of inter-domain cross talk upon NO binding.
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DOI：
10.1016/j.jmgm.2019.04.009
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发表时间：
2019-07
影响因子：
2.9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Khalid RR;Maryam A;Fadouloglou VE;Siddiqi AR;Zhang Y
人可溶性鸟苷酸环化酶（hsGC）是一种异二聚体含血红素的酶，它调节许多重要的生理过程。在真核生物中，hsGC是唯一已知的一氧化氮（NO）信号的受体。不适当的NO信号导致各种疾病，如神经变性、高血压、中风和勃起功能障碍。为了了解这些疾病的机制，确定hsGC二聚体复合物的结构是至关重要的。然而，到目前为止，所有的实验结构测定的尝试都是不成功的。目前的研究探索了利用最先进的蛋白质结构预测工具和低温电镜实验数据相结合的混合方法来模拟hsGC四级结构的可能性。由此产生的3D模型与从生物化学实验数据中提取的结构和功能见解密切一致。总之，在原子水平上确定hsGC复合物结构有助于揭示NO结合时的结构域间通讯，这对于阐明这一重要酶的生物学功能和开发针对hsGC相关人类疾病的新疗法具有重要意义。
The human soluble Guanylate Cyclase (hsGC) is a heterodimeric heme-containing enzyme which regulates many important physiological processes. In eukaryotes, hsGC is the only known receptor for nitric oxide (NO) signaling. Improper NO signaling results in various disease conditions such as neurodegeneration, hypertension, stroke and erectile dysfunction. To understand the mechanisms of these diseases, structure determination of the hsGC dimer complex is crucial. However, so far all the attempts for the experimental structure determination of the protein were unsuccessful. The current study explores the possibility to model the quaternary structure of hsGC using a hybrid approach that combines state-of-the-art protein structure prediction tools with cryo-EM experimental data. The resultant 3D model shows close consistency with structural and functional insights extracted from biochemistry experiment data. Overall, the atomic-level complex structure determination of hsGC helps to unveil the inter-domain communication upon NO binding, which should be of important usefulness for elucidating the biological function of this important enzyme and for developing new treatments against the hsGC associated human diseases.
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影响因子：
3.7
作者：
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通讯作者：
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作者：
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DOI：
10.1016/j.niox.2018.04.008
发表时间：
2018-07-01
期刊：
Nitric oxide : biology and chemistry
影响因子：
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作者：
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通讯作者：
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DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
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