Protein kinases have very dynamic structures and their functionality strongly depends on their dynamic state. Active kinases reveal a dynamic pattern with residues clustering into semirigid communities that move in μs-ms timescale. Previously detected hydrophobic spines serve as connectors between communities. Communities do not follow the traditional subdomain structure of the kinase core or its secondary structure elements. Instead they are organized around main functional units. Integration of the communities depends on the assembly of the hydrophobic spine and phosphorylation of the activation loop. Single mutations can significantly disrupt the dynamic infrastructure and thereby interfere with long-distance allosteric signaling that propagates throughout the whole molecule. Dynamics is proposed to be the underlying mechanism for allosteric regulation in protein kinases.
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http://dx.doi.org/10.1016/j.tibs.2015.09.002 | DOI Listing |
Front Immunol
January 2025
Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
As an antibody-drug conjugate (ADC), disitamab vedotin (RC48) is a promising treatment targeting ERBB2 for locally advanced and metastatic bladder cancer (BLCA). However, the subtype heterogeneity of muscle-invasive bladder cancer (MIBC) often leads to different therapeutic outcomes. In our study, we aim to explore sensitivity differences and mechanisms of different molecular subtypes of MIBC to RC48 treatment and develop a strategy for combination therapy against cancer.
View Article and Find Full Text PDFPathol Oncol Res
January 2025
Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
The () gene family is of rising importance as their fusions are oncogenic, and specific target drugs are available to inhibit the chimera proteins. Pan-TRK antibody, which shows the overexpression of the genes, is a useful tool to detect tumors with or without gene alterations, due to high negative predictive value. Though it is well known that pan-TRK immunopositivity is usually not connected to fusion, the role of other possible genetic alterations is under-researched.
View Article and Find Full Text PDFArthritis Res Ther
January 2025
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Background: Rheumatoid arthritis (RA) is a systemic disease that primarily manifests as chronic synovitis of the symmetric small joints. Despite the availability of various targeted drugs for RA, these treatments are limited by adverse reactions, warranting new treatment approaches. Suberosin (SBR), isolated from Plumbago zeylanica-a medicinal plant traditionally used to treat RA in Asia-possesses notable biological activities.
View Article and Find Full Text PDFBMC Med
January 2025
Department of Cardiothoracic Surgery, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215000, China.
Background: Current research underscores the need to better understand the pathogenic mechanisms and treatment strategies for idiopathic pulmonary fibrosis (IPF). This study aimed to identify key targets involved in the progression of IPF.
Methods: We employed Mendelian randomization (MR) with three genome-wide association studies and four quantitative trait loci datasets to identify key driver genes for IPF.
BMC Mol Cell Biol
January 2025
Department of Ultrasound, Henan Provincial People's Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan, 450000, China.
Background: Papillary thyroid carcinoma (PTC) is a common malignant tumor. BRAF mutation has become a common molecular event in PTC pathogenesis. Circular RNA PSD3 (circPSD3) is known to be highly expressed in PTC.
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