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

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 ? and ? 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 ?1 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 ?1 H-NOX domain. It also reveals a small internal cavity that may serve to bind ligands or participate in signal transduction.

SUBMITTER: Purohit R

PROVIDER: S-EPMC3795502 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Purohit Rahul R Weichsel Andrzej A Montfort William R WR

Protein science : a publication of the Protein Society 20130907 10

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 s ...[more]

PMID: 23934793

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PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure.

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