Crystal structure of the Alpha subunit PAS domain from soluble guanylyl cyclase.
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.
Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, 85721.
Rahul
R
Purohit
Andrzej
A
Weichsel
William R
WR
Montfort
D000818:Animals; D018360:Crystallography, X-Ray; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D018402:Manduca / Q000201:enzymology*; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
D008024:Ligands; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006418:Heme; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
Manduca sexta; X-ray crystallography; YC-1; nitric oxide; per-ARNT-sim domain; soluble guanylate cyclase