SHP2-E76K, a mutant encoded by the PTPN11 gene, was associated with various solid tumors, such as lung cancer, glioblastoma, and intellectual disability. SHP2-E76K has become potential drug targets, while there was no effective inhibitor against the mutant currently. At present, the crystal complex structure of SHP099 with SHP2-E76K has been reported in the RCSB PDB protein data bank, however, the dynamic structure of SHP099 binding to the active center of SHP2-E76K protein was still lacking. Therefore, this study used molecular dynamics simulation and Markov model to characterize the kinetics of the inhibitor SHP099 with SHP2-E76K enzyme and to determine the active binding site, which would give a hint of a vital enzyme-substrate interaction in atomistic detail that proposed the potential to be applied for the discovery of more effective SHP2-E76K inhibitors and, in broader terms, dynamic protein-drug interactions.
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http://dx.doi.org/10.1080/07391102.2024.2431193 | DOI Listing |
Parasitol Res
December 2024
Department of Parasitology and Parasitic Diseases, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Calea Manaștur 3-5, 400372, Cluj-Napoca, Romania.
This is the first study that targets the epidemiology of Gasterophilus spp. in slaughtered horses from Romania. Previously to our research, there were five recorded species: Gasterophilus haemorrhoidalis, Gasterophilus inermis, Gasterophilus intestinalis, Gasterophilus nasalis, and Gasterophilus pecorum with a dispersed distribution throughout the country, the data being recorded more than 73 years ago.
View Article and Find Full Text PDFJ Comput Chem
January 2025
Laboratoire d'Optique et Biosciences (CNRS UMR7645, INSERM U1182), Ecole Polytechnique, Institut polytechnique de Paris, Palaiseau, France.
Folates comprise a crucial class of biologically active compounds related to folic acid, playing a vital role in numerous enzymatic reactions. One-carbon metabolism, facilitated by the folate cofactor, supports numerous physiological processes, including biosynthesis, amino acid homeostasis, epigenetic maintenance, and redox defense. Folates share a common pterin heterocyclic ring structure capable of undergoing redox reactions and existing in various protonation states.
View Article and Find Full Text PDFNat Cancer
December 2024
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA. Electronic address:
The sarco(endo)plasmic reticulum Ca ATPase (SERCA) is a membrane transporter that creates and maintains intracellular Ca stores. In the heart, SERCA is regulated by an inhibitory interaction with the monomeric form of the transmembrane micropeptide phospholamban (PLB). PLB also forms avid homo-pentamers, and dynamic exchange of PLB between pentamers and SERCA is an important determinant of cardiac responsiveness to exercise.
View Article and Find Full Text PDFChemosphere
December 2024
Department of Biology, Faculty of Science, Shahrekord University, Shahrekord, P. O. Box.115, Iran; Central Laboratory, Shahrekord University, Shahrekord, Iran. Electronic address:
The binding interaction of food preservatives and pesticides has emerged as a matter of paramount importance as it not only presents potential health hazards but also carries substantial consequences for food processing and preservation. Herein, the mechanism of interaction between lysozyme and Amitraz was explored through spectroscopic and computational techniques. Spectral investigations indicated the spontaneous nature and stability of the lysozyme-Amitraz complex.
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