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A molecular view of the regulation of sGC activity

  • Michael A Marletta1, 2Email author,
  • Emily R Derbyshire2,
  • W Kaya Erbil1,
  • Nathaniel B Fernhoff2,
  • John Kuriyan1, 2,
  • Charles OleaJr2,
  • Mark S Price2 and
  • David E Wemmer1
BMC Pharmacology20099(Suppl 1):S27

Published: 11 August 2009


NucleotideSequence AnalysisCatalytic DomainNucleotide BindingStructural Result
Mammalian sGC is a heterodimer composed of α- and β-subunits (Figure 1). The C-terminus of each subunit contains a catalytic domain and the active site is composed of residues from both subunits. The catalytic domains also form a pseudosymmetric active site that contains residues known to be involved in nucleotide binding, but lack the amino acids required for catalysis. Sequence analysis shows that each subunit also contains well-defined PAS-like domain, and a predicted helical region. The N-termini of the α- and β-subunits are homologous to the H-NOX (H eme-N itric oxide/OX ygen) family of proteins. The N-terminus of β-subunit contains a ferrous heme cofactor that serves a receptor for NO. sGC activity is also modulated by ATP and the substrate GTP and recent studies point toward a more complicated role for NO in the regulation of activity. Structural results coupled with biochemical and cellular experiments have broadened the current molecular view of the regulation of sGC.
Figure 1

Domain structure of sGC.

Authors’ Affiliations

Department of Chemistry, University of California, Berkeley, USA
Department of Molecular and Cell Biology, University of California, Berkeley, USA


© Marletta et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.