Insights into Soluble Guanylyl Cyclase Activation Derived from Improved Heme-Mimetics
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- 作者：Margarete von Wantoch Rekowski ; Vijay Kumar ; Zongmin Zhou ; Johann Moschner ; Antonia Marazioti ; Marina Bantzi ; Georgios A. Spyroulias ; Focco van den Akker ; Athanassios Giannis ; Andreas Papapetropoulos
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：November 14, 2013
- 年：2013
- 卷：56
- 期：21
- 页码：8948-8952
- 全文大小：312K
- 年卷期：v.56,no.21(November 14, 2013)
- ISSN：1520-4804
文摘
Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of 伪F helix containing 110鈥?14 residues contributes to the higher activation triggered by 20.