scholarly journals Solution structures of the Shewanella woodyi H‐NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP ‐051

2020 ◽  
Vol 30 (2) ◽  
pp. 448-463
Author(s):  
Cheng‐Yu Chen ◽  
Woonghee Lee ◽  
Paul A. Renhowe ◽  
Joon Jung ◽  
William R. Montfort
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Solution Structures ◽  
Shewanella Woodyi ◽  
Presence And Absence

scholarly journals Solution structures of the Shewanella woodyi H-NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP-051

2020 ◽  
Author(s):  
Cheng-Yu Chen ◽  
Woonghee Lee ◽  
William R. Montfort
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Guanylyl Cyclase ◽  
Critical Role ◽  
Coiled Coil ◽  
Soluble Guanylyl Cyclase ◽  
Binding Pocket ◽  
Backbone Dynamics ◽  
Shewanella Woodyi ◽  
Presence And Absence

AbstractHeme-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. Non-planar 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. Binding lead to rotation of the subdomains and closure of the binding pocket. Backbone dynamics for the protein 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.

scholarly journals Maturation, inactivation, and recovery mechanisms of soluble guanylyl cyclase

2021 ◽  
Vol 296 ◽  
pp. 100336
Author(s):  
Dennis J. Stuehr ◽  
Saurav Misra ◽  
Yue Dai ◽  
Arnab Ghosh
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Recovery Mechanisms

scholarly journals Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons

2020 ◽  
Author(s):  
Thomas J Pirtle ◽  
Richard A Satterlie
Keyword(s):  
Nitric Oxide ◽  
Central Pattern Generator ◽  
Guanylyl Cyclase ◽  
Signal Transduction Pathway ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Pattern Generator ◽  
Guanosine Monophosphate ◽  
Cellular Changes ◽  
Clione Limacina

Abstract Typically, the marine mollusk, Clione limacina, exhibits a slow, hovering locomotor gait to maintain its position in the water column. However, the animal exhibits behaviorally relevant locomotor swim acceleration during escape response and feeding behavior. Both nitric oxide and serotonin mediate this behavioral swim acceleration. In this study, we examine the role that the second messenger, cGMP, plays in mediating nitric oxide and serotonin-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase increased fictive locomotor speed recorded from Pd-7 interneurons of the animal’s locomotor central pattern generator. Moreover, inhibition of soluble guanylyl cyclase decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because nitric oxide has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by serotonin application, we hypothesize that both nitric oxide and serotonin function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates nitric oxide-induced but not serotonin-induced swim acceleration in Clione.

scholarly journals Insights into Soluble Guanylyl Cyclase Activation Derived from Improved Heme-Mimetics

2013 ◽  
Vol 56 (21) ◽  
pp. 8948-8952 ◽  
Author(s):  
Margarete von Wantoch Rekowski ◽  
Vijay Kumar ◽  
Zongmin Zhou ◽  
Johann Moschner ◽  
Antonia Marazioti ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cyclase Activation

scholarly journals Nitric Oxide Activates the β2Subunit of Soluble Guanylyl Cyclase in the Absence of a Second Subunit

2001 ◽  
Vol 276 (33) ◽  
pp. 30737-30743 ◽  
Author(s):  
Markus Koglin ◽  
Kai Vehse ◽  
Lars Budaeus ◽  
Hasso Scholz ◽  
Sönke Behrends
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase

scholarly journals Glutamate regulates Ca2+ signals in smooth muscle cells of newborn piglet brain slice arterioles through astrocyte- and heme oxygenase-dependent mechanisms

2010 ◽  
Vol 298 (2) ◽  
pp. H562-H569 ◽  
Author(s):  
Qi Xi ◽  
Edward Umstot ◽  
Guiling Zhao ◽  
Damodaran Narayanan ◽  
Charles W. Leffler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Heme Oxygenase ◽  
Guanylyl Cyclase ◽  
Brain Slices ◽  
Soluble Guanylyl Cyclase ◽  
Muscle Cells ◽  
Newborn Piglet ◽  
Signal Modulation ◽  
Cerebral Arterioles

Glutamate is the principal cerebral excitatory neurotransmitter and dilates cerebral arterioles to match blood flow to neural activity. Arterial contractility is regulated by local and global Ca2+ signals that occur in smooth muscle cells, but modulation of these signals by glutamate is poorly understood. Here, using high-speed confocal imaging, we measured the Ca2+ signals that occur in arteriole smooth muscle cells of newborn piglet tangential brain slices, studied signal regulation by glutamate, and investigated the physiological function of heme oxygenase (HO) and carbon monoxide (CO) in these responses. Glutamate elevated Ca2+ spark frequency by ∼188% and reduced global intracellular Ca2+ concentration ([Ca2+]i) to ∼76% of control but did not alter Ca2+ wave frequency in brain arteriole smooth muscle cells. Isolation of cerebral arterioles from brain slices abolished glutamate-induced Ca2+ signal modulation. In slices treated with l-2-α-aminoadipic acid, a glial toxin, glutamate did not alter Ca2+ sparks or global [Ca2+]i but did activate Ca2+ waves. This shift in Ca2+ signal modulation by glutamate did not occur in slices treated with d-2-α-aminoadipic acid, an inactive isomer of l-2-α-aminoadipic acid. In the presence of chromium mesoporphyrin, a HO blocker, glutamate inhibited Ca2+ sparks and Ca2+ waves and did not alter global [Ca2+]i. In isolated arterioles, CORM-3 [tricarbonylchloro(glycinato)ruthenium(II)], a CO donor, activated Ca2+ sparks and reduced global [Ca2+]i. These effects were blocked by 1 H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one, a soluble guanylyl cyclase inhibitor. Collectively, these data indicate that glutamate can modulate Ca2+ sparks, Ca2+ waves, and global [Ca2+]i in arteriole smooth muscle cells via mechanisms that require astrocytes and HO. These data also indicate that soluble guanylyl cyclase is involved in CO activation of Ca2+ sparks in arteriole smooth muscle cells.

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