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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzoates / chemical synthesis
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Benzoates / chemistry
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Benzoates / pharmacology*
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Dose-Response Relationship, Drug
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Drug Design
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Enzyme Activation
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Guanylate Cyclase / metabolism*
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Heme / chemistry
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Heme / metabolism*
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Models, Molecular
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Molecular Conformation / drug effects
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Nitric Oxide / metabolism
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Nostoc / enzymology
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Soluble Guanylyl Cyclase
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Structure-Activity Relationship
Substances
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Benzoates
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Receptors, Cytoplasmic and Nuclear
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Nitric Oxide
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BAY 58-2667
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Heme
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Guanylate Cyclase
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Soluble Guanylyl Cyclase