Guanylyl cyclase: NO hits its target.
The NO receptor, NO-sensitive guanylyl cyclase, plays a key role in the NO/cGMP signal-transduction cascade. Two isoforms of the enzyme are currently known, the widely distributed vascular alpha1beta1 isoform and the neuronal alpha2beta1 isoform predominantly expressed in brain. Interaction with the PSD-95 (postsynaptic density protein-95) family of scaffolding proteins targets the neuronal alpha2beta1 isoform to synaptic membranes. The NO sensor of the guanylyl cyclase is formed by the prosthetic haem group, where NO binding takes place and induces the up to 200-fold activation of the enzyme. The haem group allows tight regulation of enzymic activity by NO and represents the most striking feature of the enzyme, as it differs in many aspects from the well-characterized haem groups of other haemoproteins. The new NO sensitizers such as YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] affect activation by NO and CO by mechanisms that are currently subject to intense research.
Russwurm
Michael
M
Pharmakologie und Toxikologie, Medizinische Fakultät MA NI, Ruhr-Universität Bochum, 44780 Bochum, Germany.
Koesling
Doris
D
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D020536:Enzyme Activators / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008956:Models, Chemical; D009569:Nitric Oxide / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D014018:Tissue Distribution
D020536:Enzyme Activators; D007527:Isoenzymes; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006418:Heme; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP