Soluble guanylate cyclase, a heterodimer consisting of an alpha- and a heme-containing beta-subunit, is the major receptor for the biological messenger nitric oxide (NO) and is involved in various signal transduction pathways. The heme moiety of the enzyme is bound between the axial heme ligand histidine(105) and the recently identified counterparts of the heme propionic acids, tyrosine(135) and arginine(139). The latter residues together with an invariant serine(137) form the unique heme binding motif Y-x-S-x-R. In this work, we show that replacement of the serine(137) with alanine destabilizes the binding of the heme moiety and impairs NO-mediated soluble guanylate cyclase activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2005.02.046 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.
Chem Biol Drug Des
January 2025
Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R side-group and R end-group interplay when the R side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R/R-phenyl inhibitors upon elongation and/or fluorination of R-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R is pyridine, the impact of R-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration.
View Article and Find Full Text PDFGiardia duodenalis flavohemoglobin is a target of 5-nitroheterocycle and benzimidazole compounds acting as enzymatic inhibitors or subversive substrates.
Free Radic Biol Med
December 2024
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados Del Instituto Politécnico Nacional, 07360, Mexico City, Mexico. Electronic address:
Giardia duodenalis causes giardiasis in humans, companion, livestock and wild animals. Control of infection involves drugs as benzimidazoles (e.g.
View Article and Find Full Text PDFSite-specific incorporation of F-nulcei at protein C-terminus to probe allosteric conformational transitions of metalloproteins.
Commun Biol
December 2024
School of Chemistry and Chemical Engineering, University of South China, Hengyang, China.
Article Synopsis
- Allosteric conformational changes in proteins are regulated by the binding of small cofactors, metal ions, or protein partners, which can now be effectively monitored using F NMR with a specific F incorporation strategy at the protein C-terminus.
- Case studies using hemoprotein neuroglobin, calmodulin, and cobalt metalloregulator show how F-nuclei near the C-terminus can reveal protein dynamics both nearby and at a distance, highlighting the unique functions and interactions in these proteins.
- The research presents a novel AEP-based F-modification method that can be applied to various proteins to explore allosteric regulation, particularly focusing on biological processes influenced by the C-terminus.
Blood matters: the hematological signatures of Coronavirus infection.
Cell Death Dis
November 2024
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses.
View Article and Find Full Text PDFHeme oxygenase 1 inhibitor discovery and formulation into nanostructured lipid carriers as potent and selective treatment against triple negative metastatic breast cancer.
Int J Pharm
January 2025
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Faculty of Pharmacy, iMATUS, and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address:
Heme oxygenase-1 (HO-1) has been identified as a potential new target in anticancer therapy, being overexpressed in different tumors and crucial for cell proliferation. Advances in the development of specific HO-1 inhibitors should support the understanding of controlling HO-1 activity as antitumoral strategies, opening the path for future therapeutic applications. In the present study, small series of new HO-1 inhibitors were synthesized by joining a butylimidazolic pharmacophore together with a hydrophobic moiety spaced by a 2-oxybenzamide central linker.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!