Crystal structure of the Alpha subunit PAS domain from soluble guanylyl cyclase

Rahul Purohit, Andrzej Weichsel, William R. Montfort

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Soluble guanylate cyclase (sGC) is a heterodimeric heme protein of ~150 kDa and the primary nitric oxide receptor. Binding of NO stimulates cyclase activity, leading to regulation of cardiovascular physiology and providing attractive opportunities for drug discovery. How sGC is stimulated and where candidate drugs bind remains unknown. The α and β sGC chains are each composed of Heme-Nitric Oxide Oxygen (H-NOX), Per-ARNT-Sim (PAS), coiled-coil and cyclase domains. Here, we present the crystal structure of the α1 PAS domain to 1.8 Å resolution. The structure reveals the binding surfaces of importance to heterodimer function, particularly with respect to regulating NO binding to heme in the β1 H-NOX domain. It also reveals a small internal cavity that may serve to bind ligands or participate in signal transduction.

Original languageEnglish (US)
Pages (from-to)1439-1444
Number of pages6
JournalProtein Science
Volume22
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • Manduca sexta
  • Nitric oxide
  • Per-ARNT-sim domain
  • Soluble guanylate cyclase
  • X-ray crystallography
  • YC-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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