NO-independent regulatory site on soluble guanylate cyclase

@article{Stasch2001NOindependentRS,
  title={NO-independent regulatory site on soluble guanylate cyclase},
  author={J-P. Stasch and Eva-Maria Becker and Cristina Alonso-Alija and Heiner Apeler and Klaus Dembowsky and Achim Feurer and Rupert Gerzer and Torsten Minuth and Elisabeth Perzborn and Ulrich Pleiss and Henning Schröder and Werner Dr Schroeder and Elke Stahl and Wolfram Steinke and Alexander T. Straub and Matthias Schramm},
  journal={Nature},
  year={2001},
  volume={410},
  pages={212-215}
}
Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric… 

Structure and regulation of soluble guanylate cyclase.

This review summarizes the current understanding of sGC structure and regulation as well as recent developments in NO signaling to aid therapeutic intervention in diseases involving the NO/cGMP-signaling pathway.

Guanylate Cyclase and Cyclic GMP

The NO/cGMP signalling cascade participates in the regulation of physiological parameters such as smooth muscle relaxation, inhibition of platelet aggregation, and neuronal transmission. cGMP is

Soluble guanylate cyclase in NO signaling transduction

The progress of sGC on structural, functional investigations, as well as the proposed activation/deactivation mechanism are reviewed, and the heme-dependent sGC stimulators and he me-independent sGC activators are summarized briefly.

Soluble Guanylyl Cyclase: Physiological Role as an NO Receptor and the Potential Molecular Target for Therapeutic Application

  • M. Nakane
  • Biology, Chemistry
    Clinical chemistry and laboratory medicine
  • 2003
The NO/cGMP signal transduction pathway is reviewed and soluble guanylyl cyclase modulators are defined as a novel approach for the treatment of cardiovascular diseases and erectile dysfunction.

NO-independent, haem-dependent soluble guanylate cyclase stimulators.

Pharmacological stimulators of sGC may be beneficial in the treatment of a range of diseases, including systemic and pulmonary hypertension, heart failure, atherosclerosis, erectile dysfunction, and renal fibrosis.

Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system.

It is concluded that the majority of NO-sensitive GC is not required for cGMP-forming activity but as NO receptor reserve to increase sensitivity toward the labile messenger NO in vivo.

The Mechanism of Allosteric Regulation in Soluble Guanylate Cyclase

This dissertation describes experiments designed to uncover the molecular basis for signal transduction in sGC by NO and small molecule stimulators and shows that the coiled coil domain plays a pocket important in allostery and drug action.
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