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Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics.

ABSTRACT: 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 αF helix containing 110-114 residues contributes to the higher activation triggered by 20.

SUBMITTER: Rekowski MVW

PROVIDER: S-EPMC3902542 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics.

Rekowski Margarete von Wantoch MVW Kumar Vijay V Zhou Zongmin Z Moschner Johann J Marazioti Antonia A Bantzi Marina M Spyroulias Georgios A GA van den Akker Focco F Giannis Athanassios A Papapetropoulos Andreas A

Journal of medicinal chemistry 20131024 21

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 αF helix containing 110-114 residues contributes to the higher acti ...[more]

PMID: 24090476

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