Protein kinases are dynamic enzymes that display complex regulatory mechanisms. Although they possess a structurally conserved catalytic domain, significant conformational dynamics are evident both within a single kinase and across different kinases in the kinome. Here, we highlight methods for exploring this conformational space and its dynamics using kinase domains from ABL1 (Abelson kinase), PKA (protein kinase A), AurA (Aurora A), and PYK2 (proline-rich tyrosine kinase 2) as examples. Such experimental approaches combined with AI-driven methods, such as AlphaFold, will yield discoveries about kinase regulation, the catalytic process, substrate specificity, the effect of disease-associated mutations, as well as new opportunities for structure-based drug design.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.sbi.2024.102890 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-throughput screening of dual-target inhibitors for SARS-CoV-2 main protease and papain-like protease from Chebulae Fructus: prediction and experimental verification.
Front Microbiol
December 2024
State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Background: The unavoidable propagation of the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has underscored the urgent requirement for efficacious therapeutic agents. The dried fruit of Retz., namely Chebulae Fructus, is widely used for treating bacterial and viral infectious diseases, which was witnessed to perform anti-SARS-CoV-2 activity in recommended Chinese patent medicine.
View Article and Find Full Text PDFMolecular dynamics of transferrin receptor binder peptides: unlocking blood-brain barrier for enhanced CNS drug delivery.
J Biomol Struct Dyn
January 2025
Laboratório de Planejamento e Desenvolvimento de Fármacos, Universidade Federal do Pará, Belem, Brazil.
A cystine-dense peptide (CDP) named TfRB1 was identified for its ability to bind to the transferrin receptor (TfR). CDPs are stabilized by their disulfide bonds, and variants of TfRB1 - specifically TfRB1G1, TfRB1G2, and TfRB1G3 - are explored for their potential to transport molecules across the blood-brain barrier (BBB) into the central nervous system (CNS). This study employed molecular modeling and dynamics simulations to characterize the interactions between these TfRB1 variants and TfR.
View Article and Find Full Text PDFSynthesis, in vivo evaluation, and in silico molecular docking of benzo[h]quinoline derivatives as potential Culex pipiens L. larvicides.
Bioorg Chem
December 2024
Chemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt. Electronic address:
A new series of benzo[h]quinoline-containing heterocycles was synthesized via reactions of benzo[h]quinolinyl-2(3H)-furanone with some nitrogen bidentate nucleophiles, leading to the formation of pyridazinone, pyrrolinone, benzimidazole, and benzoxazinone derivatives. The synthesized compounds were evaluated for their insecticidal activity against Culex pipiens L. larvae.
View Article and Find Full Text PDFZinc finger proteins facilitate adaptation of a global insect pest to climate change.
BMC Biol
December 2024
State Key Laboratory for Ecological Pest Control of Fujian and Taiwan Crops, Institute of Applied Ecology, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Background: Global climate change significantly impacts ecosystems, particularly through temperature fluctuations that affect insect physiology and behavior. As poikilotherms, insect pests such as the globally devastating diamondback moth (DBM), Plutella xylostella, are especially vulnerable to rising temperatures and extreme heat events, necessitating effective adaptive mechanisms.
Results: Here we demonstrate the roles of zinc finger proteins (ZFPs) in mediating thermal adaptability in DBM.
Mutations of the CEACAM5 Gene PELPK Motif in Patients With Appendiceal or Colorectal Adenocarcinoma.
In Vivo
December 2024
Liver & Peritonectomy Unit, Department of Surgery, St George Hospital, Kogarah, NSW, Australia.
Background/aim: The study examines whether DNA level mutations in the carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) gene Pro-Glu-Leu-Pro-Lys (PELPK) motif differ between patients with appendiceal or colorectal adenocarcinoma. Significant differences between these two groups in correlation with development of metachronous liver metastases could help in the development of targeted therapies and preventative treatment approaches.
Patients And Methods: This retrospective comparative trial analysed 18 patients, 9 with appendiceal adenocarcinoma and 9 with colorectal adenocarcinoma.
Want 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!