By Alexander Y. Kots, Emil Martin, Iraida G. Sharina, Ferid Murad (auth.), Harald H. H. W. Schmidt, Franz Hofmann, Johannes-Peter Stasch (eds.)
After the invention of endogenous NO formation within the overdue '80s and the 1998 Nobel Prize in body structure or medication, many researchers and physicians back got interested within the NO/sGC interplay and cGMP-dependent signaling. This publication is an enthusiastic party of cyclic guanosine monophosphate (cGMP) and amply illustrates the significance of this box of technology to sufferers and how within which the sector has advanced. it's completely dedicated to this fascinating and critical signaling molecule, addressing all contemporary advances in figuring out guanylate cyclase rules, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. specific recognition can be given to medical purposes of the radical cGMP-elevating medications that are at the horizon, hence spanning the continuum from uncomplicated technology to clinic.
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Additional info for cGMP: Generators, Effectors and Therapeutic Implications
In facultative aerobes the bacterial members of this family encode a single domain as a stand-alone protein, and genes that encode for either putative histidine kinases or diguanylate cyclases are found in the same predicted operon. This suggests that the domain has a role in two-component signaling in bacteria. In support of this hypothesis, an H-NOX domain and a predicted histidine kinase from Shewanella oneidensis were isolated and found to interact in vitro. Additionally, the functional interaction between the H-NOX and kinase was mediated by NO (Price et al.
1997), and the EPR spectrum of the FeII -NO complex shifts to a unique signal with either GTP or YC-1 addition (Derbyshire et al. 2008; Makino et al. 2003). This indicates that there are at least two sGC FeII -NO conformations of differing activities, and that the abundance of each conformation is influenced by both substrate and activator binding. This proposal is further supported by NO dissociation experiments which show that the sGC ferrous nitrosyl complex adopts two 5-coordinate conformations that are influenced by the presence of GTP and YC-1; a lower-activity complex which releases NO slowly and a higher-activity complex which releases NO rapidly (Winger et al.
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