Key result
Mutation of two cysteines of the beta1 subunit (Cys-78 and Cys-214) of soluble guanylyl cyclase reduced the affinity for heme and yielded proteins insensitive to NO.
Population
Recombinant soluble guanylyl cyclase (sGC) enzymes expressed in Sf9 cells
Comparison
Site-directed mutagenesis of 15 conserved… vs Wild-type sGC and mutations on the alpha1 subunit
Design
Preclinical
Authors
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Mutating conserved cysteines clarifies sGC regulation; leaves open new cGMP pathway targets for cardiovascular therapies.
Conserved cysteines Cys-78 and Cys-214 on the beta1 subunit of soluble guanylyl cyclase are essential for heme binding and NO-stimulated cGMP synthesis.
Friebe et al. (1997) studied this question. Site-directed mutagenesis of conserved cysteine residues to serine vs. Wild-type sGC / corresponding cysteines on alpha1 subunit was evaluated on cGMP synthesis, NO sensitivity, and heme binding. Mutation of two cysteines of the beta1 subunit (Cys-78 and Cys-214) of soluble guanylyl cyclase reduced the affinity for heme and yielded proteins insensitive to NO.
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