A hydrogen bond network has been identified that adjusts protein-substrate contacts in cytochrome P450(cam) (CYP101A1). Replacing the native substrate camphor with adamantanone or norcamphor causes perturbations in NMR-detected NH correlations assigned to the network, which includes portions of a β sheet and an adjacent helix that is remote from the active site. A mutation in this helix reduces enzyme efficiency and perturbs the extent of substrate-induced spin state changes at the haem iron that accompany substrate binding. In turn, the magnitude of the spin state changes induced by alternate substrate binding parallel the NMR-detected perturbations observed near the haem in the enzyme active site.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071453 | PMC |
| http://dx.doi.org/10.1039/c0mt00065e | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of potent schistosomicidal compounds predicted as type II-kinase inhibitors against c-Jun N-terminal kinase SMJNK.
Front Parasitol
April 2024
Institut für Parasitologie, Biomedizinisches Forschungszentrum Seltersberg (BFS), Justus Liebig Universitaet Giessen, Giessen, Germany.
Introduction: Schistosomiasis has for many years relied on a single drug, praziquantel (PZQ) for treatment of the disease. Immense efforts have been invested in the discovery of protein kinase (PK) inhibitors; however, given that the majority of PKs are still not targeted by an inhibitor with a useful level of selectivity, there is a compelling need to expand the chemical space available for synthesizing new, potent, and selective PK inhibitors. Small-molecule inhibitors targeting the ATP pocket of the catalytic domain of PKs have the potential to become drugs devoid of (major) side effects, particularly if they bind selectively.
View Article and Find Full Text PDFDetecting two circulating antigens - CCA and CAA - in urine and serum to improve diagnosis of human schistosomiasis.
Front Parasitol
October 2024
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Background: Schistosomiasis is caused by infection with parasitic worms and affects more than 250 million people globally. The detection of schistosome derived circulating cathodic and anodic antigens (CCA and CAA) has proven highly valuable for detecting active infections, causing both intestinal and urinary schistosomiasis.
Aim: The combined detection of CCA and CAA was explored to improve accuracy in detecting infections.
Thiol-Reactive or Redox-Active: Revising a Repurposing Screen Led to a New Invalidation Pipeline and Identified a True Noncovalent Inhibitor Against Papain-like Protease from SARS-CoV-2.
ACS Pharmacol Transl Sci
January 2025
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, Schnackenburgallee 114, 22525 Hamburg, Germany.
The SARS-CoV-2 papain-like protease PLpro has multiple roles in the viral replication cycle, related to both its polypeptide cleavage function and its ability to antagonize the host immune response. Targeting the PLpro function is recognized as a promising mechanism to modulate viral replication, while supporting host immune responses. However, the development of PLpro-specific inhibitors remains challenging.
View Article and Find Full Text PDFLipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.
Brain Commun
January 2025
Neuromuscular Department, Motor Neuron Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS.
View Article and Find Full Text PDFIn silico analysis of -derived peptides and plasmid construction for recombinant anti-aging therapies.
Narra J
December 2024
Department of Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Skin aging is one of the degenerative processes influenced by tyrosinase, elastase, collagenase, hyaluronidase, and matrix metalloproteinase-9 (MMP9) activity. One promising avenue for discovering antiaging therapeutics is the peptides from the spine. The aim of this study was to explore the potential of peptides from spine as a multitarget inhibitor for recombinant antiaging therapies through in silico approaches.
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!