Protein kinase A (PKA) is a ubiquitous phosphoryl transferase that mediates hundreds of cell signaling events. During turnover, its catalytic subunit (PKA-C) interconverts between three major conformational states (open, intermediate, and closed) that are dynamically and allosterically activated by nucleotide binding. We show that the structural transitions between these conformational states are minimal and allosteric dynamics encode the motions from one state to the next. NMR and molecular dynamics simulations define the energy landscape of PKA-C, with the substrate allowing the enzyme to adopt a broad distribution of conformations (dynamically committed state) and the inhibitors (high magnesium and pseudosubstrate) locking it into discrete minima (dynamically quenched state), thereby reducing the motions that allow turnover. These results unveil the role of internal dynamics in both kinase function and regulation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084134 | PMC |
| http://dx.doi.org/10.1073/pnas.1102701108 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploring the motivations and dynamics of older French-speaking men settled in Thailand.
Cult Health Sex
January 2025
Department of Management, Bogazici University, Istanbul, Türkiye.
This paper examines the motivations and experiences of older French-speaking men who relocate to Thailand driven by the desire for a more fulfilling and liberated lifestyle that contrasts with their experiences in their home countries. Through an analysis of video interviews with 31 expatriates available online, the study reveals a prevalent trend among these men to initially engage in short-term sexual relationships, enjoying the freedoms of Thailand's vibrant social scene. However, as they acclimate to their new environment, a significant shift towards long-term partnerships is observed, marking a transition from transient interactions to more meaningful connections.
View Article and Find Full Text PDFAssessing the Burden of Neglected Tropical Diseases in Low-Income Communities: Challenges and Solutions.
Viruses
December 2024
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
Neglected tropical diseases (NTDs) represent a group of chronic and debilitating infections that affect more than one billion people, predominantly in low-income communities with limited health infrastructure. This paper analyzes the factors that perpetuate the burden of NTDs, highlighting how poor health infrastructure, unfavorable socioeconomic conditions and lack of therapeutic resources exacerbate their impact. The effectiveness of current interventions, such as mass drug administration (MDA) programs and improved sanitation, in reducing disease prevalence is examined.
View Article and Find Full Text PDFCryo-EM analysis of complement C3 reveals a reversible major opening of the macroglobulin ring.
Nat Struct Mol Biol
January 2025
Department of Molecular Biology and Genetics, Aarhus, Denmark.
The C3 protein is the central molecule within the complement system and undergoes proteolytic activation to C3b in the presence of pathogens. Pattern-independent activation of C3 also occurs via hydrolysis, resulting in C3(HO), but the structural details of C3 hydrolysis remain elusive. Here we show that the conformation of the C3(HO) analog, C3MA, is indistinguishable from C3b.
View Article and Find Full Text PDFDeciphering the abnormal IR spectral density of phthalic acid dimer crystals: Unveiling the role of the dynamical effects of the Davydov coupling and the mechanisms of relaxation.
Spectrochim Acta A Mol Biomol Spectrosc
January 2025
Physics Department, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia. Electronic address:
To consistently determine the anomalous characteristics of phthalic acid crystal (PAC) derivatives, we performed quantum dynamics simulations of the infrared spectral density of the h-PAC and d-PAC isotopomers that show up in the H/D isotopic frequency domain at two different temperatures viz. 77 and 298 K. A theoretical framework explaining the dynamical cooperative interactions within the hydrogen bonds (HBs) in the PAC crystals across a simulation of IR spectral density of the stretching band was developed.
View Article and Find Full Text PDFBasal ganglia components have distinct computational roles in decision-making dynamics under conflict and uncertainty.
PLoS Biol
January 2025
Carney Institute for Brain Science, Department of Cognitive & Psychological Sciences, Brown University, Providence, Rhode Island, United States of America.
The basal ganglia (BG) play a key role in decision-making, preventing impulsive actions in some contexts while facilitating fast adaptations in others. The specific contributions of different BG structures to this nuanced behavior remain unclear, particularly under varying situations of noisy and conflicting information that necessitate ongoing adjustments in the balance between speed and accuracy. Theoretical accounts suggest that dynamic regulation of the amount of evidence required to commit to a decision (a dynamic "decision boundary") may be necessary to meet these competing demands.
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!