Nucleotidyl cyclase activity of soluble guanylyl cyclase α1β1

Biochemistry. 2012 Jan 10;51(1):194-204. doi: 10.1021/bi201259y. Epub 2011 Dec 13.


Soluble guanylyl cyclase (sGC) regulates several important physiological processes by converting GTP into the second-messenger cGMP. sGC has several structural and functional properties in common with adenylyl cyclases (ACs). Recently, we reported that membranous ACs and sGC are potently inhibited by 2',3'-O-(2,4,6-trinitrophenyl)-substituted purine and pyrimidine nucleoside 5'-triphosphates. Using a highly sensitive high-performance liquid chromatography-tandem mass spectrometry method, we report that highly purified recombinant sGC of rat possesses nucleotidyl cyclase activity. As opposed to GTP, ITP, XTP and ATP, the pyrimidine nucleotides UTP and CTP were found to be sGC substrates in the presence of Mn(2+). When Mg(2+) is used, sGC generates cGMP, cAMP, cIMP, and cXMP. In conclusion, soluble "guanylyl" cyclase possesses much broader substrate specificity than previously assumed. Our data have important implications for cyclic nucleotide-mediated signal transduction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cyclic AMP / chemistry
  • Cyclic CMP / chemistry
  • Cyclic GMP / chemistry
  • Cyclic IMP / chemistry
  • Guanylate Cyclase / chemistry*
  • Guanylate Cyclase / metabolism
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Ligases / chemistry*
  • Ligases / metabolism
  • Rats
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Ribonucleotides / chemistry
  • Solubility
  • Soluble Guanylyl Cyclase
  • Substrate Specificity
  • Xanthine


  • Isoenzymes
  • Receptors, Cytoplasmic and Nuclear
  • Ribonucleotides
  • Xanthine
  • Cyclic IMP
  • Cyclic CMP
  • xanthosine monophosphate
  • Cyclic AMP
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Ligases
  • RNA 3'-terminal phosphate cyclase
  • Cyclic GMP