6OCV

Solution structure of the H-NOX protein from Shewanella woodyi in the Fe(II)CO ligation state

Summary for 6OCV

• Entry DOI: 10.2210/pdb6ocv/pdb
• NMR Information: BMRB: 27284
• Descriptor: Heme NO binding domain protein, CARBON MONOXIDE, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: hemoprotein, nitric oxide, signaling, signaling protein
• Biological source: Shewanella woodyi
• Total number of polymer chains: 1
• Total formula weight: 22412.04

Authors

Chen, C.Y.,Lee, W.,Montfort, W.R. (deposition date: 2019-03-25, release date: 2020-05-06, Last modification date: 2024-05-01)

Primary citation

Chen, C.Y.,Lee, W.,Renhowe, P.A.,Jung, J.,Montfort, W.R.
Solution structures of the Shewanella woodyi H-NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP-051.
Protein Sci., 30:448-463, 2021

PubMed Abstract: Heme-nitric oxide/oxygen binding (H-NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacterium Shewanella woodyi (Sw), H-NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H-NOX domain to induce cyclase activity and regulate vascular tone, wound healing and memory formation. sGC also binds stimulator compounds targeting cardiovascular disease. The molecular details of stimulator binding to sGC remain obscure but involve a binding pocket near an interface between H-NOX and coiled-coil domains. Here, we report the full NMR structure for CO-ligated Sw H-NOX in the presence and absence of stimulator compound IWP-051, and its backbone dynamics. Nonplanar heme geometry was retained using a semi-empirical quantum potential energy approach. Although IWP-051 binding is weak, a single binding conformation was found at the interface of the two H-NOX subdomains, near but not overlapping with sites identified in sGC. Binding leads to rotation of the subdomains and closure of the binding pocket. Backbone dynamics are similar across both domains except for two helix-connecting loops, which display increased dynamics that are further enhanced by compound binding. Structure-based sequence analyses indicate high sequence diversity in the binding pocket, but the pocket itself appears conserved among H-NOX proteins. The largest dynamical loop lies at the interface between Sw H-NOX and its binding partner as well as in the interface with the coiled coil in sGC, suggesting a critical role for the loop in signal transduction.

PubMed: 33236796
DOI: 10.1002/pro.4005

Experimental method

SOLUTION NMR