ArticleBiochemistry2014
Interfacial residues promote an optimal alignment of the catalytic center in human soluble guanylate cyclase: heterodimerization is required but not sufficient for activity.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Architecture and activation of single-pass transmembrane receptor guanylyl cyclase.Nature structural & molecular biology · 2025Article
- On the Origins of Enzymes: Phosphate-Binding Polypeptides Mediate Phosphoryl Transfer to Synthesize Adenosine Triphosphate.Journal of the American Chemical Society · 2023Article
- Strategies of Pathogens to Escape from NO-Based Host Defense.Antioxidants (Basel, Switzerland) · 2022Review
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Current Modulation of Guanylate Cyclase Pathway Activity-Mechanism and Clinical Implications.Molecules (Basel, Switzerland) · 2021Review
- Structural Perspectives on the Mechanism of Soluble Guanylate Cyclase Activation.International journal of molecular sciences · 2021Review
- Selective cysteines oxidation in soluble guanylyl cyclase catalytic domain is involved in NO activation.Free radical biology & medicine · 2021Article
- Molecular basis for GTP recognition by light-activated guanylate cyclase RhGC.The FEBS journal · 2020Article
- Synergistic mutations in soluble guanylyl cyclase (sGC) reveal a key role for interfacial regions in the sGC activation mechanism.The Journal of biological chemistry · 2019Article
- Article
- Instability in a coiled-coil signaling helix is conserved for signal transduction in soluble guanylyl cyclase.Protein science : a publication of the Protein Society · 2019Article
- Article
- Physiological activation and deactivation of soluble guanylate cyclase.Nitric oxide : biology and chemistry · 2018Review
- Structure/function of the soluble guanylyl cyclase catalytic domain.Nitric oxide : biology and chemistry · 2018Review
- Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex.Journal of the American Society for Mass Spectrometry · 2018Article
- Molecular docking analysis of phytoconstituent from Momordica charantia with Guanylate Cyclase catalytic domain.Bioinformation · 2018Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor.Antioxidants & redox signaling · 2017Review
- The Role of Reactive Oxygen and Nitrogen Species in the Expression and Splicing of Nitric Oxide Receptor.Antioxidants & redox signaling · 2017Review
- Inhibition of soluble guanylyl cyclase by small molecules targeting the catalytic domain.FEBS letters · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Soluble guanylate cyclase (sGC) plays a central role in the cardiovascular system and is a drug target for the treatment of pulmonary hypertension. While the three-dimensional structure of sGC is unknown, studies suggest that binding of the regulatory domain to the catalytic domain maintains sGC in an autoinhibited basal state. The activation signal, binding of NO to heme, is thought to be transmitted via the regulatory and dimerization domains to the cyclase domain and unleashes the full catalytic potential of sGC. Consequently, isolated catalytic domains should show catalytic turnover comparable to that of activated sGC. Using X-ray crystallography, activity measurements, and native mass spectrometry, we show unambiguously that human isolated catalytic domains are much less active than basal sGC, while still forming heterodimers. We identified key structural elements regulating the dimer interface and propose a novel role for residues located in an interfacial flap and a hydrogen bond network as key modulators of the orientation of the catalytic subunits. We demonstrate that even in the absence of the regulatory domain, additional sGC domains are required to guide the appropriate conformation of the catalytic subunits associated with high activity. Our data support a novel regulatory mechanism whereby sGC activity is tuned by distinct domain interactions that either promote or inhibit catalytic activity. These results further our understanding of heterodimerization and activation of sGC and open additional drug discovery routes for targeting the NO-sGC-cGMP pathway via the design of small molecules that promote a productive conformation of the catalytic subunits or disrupt inhibitory domain interactions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.