A theory of the ground state's destabilization is developed explaining the high efficiency of proteases. The theory suggests a participation of the valence interactions in the formation of a productive complex and connects the efficiency and the specificity of proteolysis with the structure of such a complex. Proved is nonproductivity of nonvalence complexes in which the reactive amide group of the substrate is planar. It is suggested that the theory of the absolute rates of reactions does not cover the process of the enzymatic hydrolysis.
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Biogerontology
January 2025
Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Aging is associated with a marked increase in cardiovascular diseases, such as myocardial infarction (MI). Cellular senescence is also a crucial factor in the development of age-related MI. Matrix metalloproteinases (MMPs) interaction with cellular senescence is a critical determinant of MI development and outcomes, most notably in the aged heart.
View Article and Find Full Text PDFFront Immunol
January 2025
Immunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Microbiology & Immunology, National University of Singapore, Singapore, Singapore.
Introduction: Collagen is essential for maintaining lung structure and function and its remodeling has been associated with respiratory diseases including chronic obstructive pulmonary disease (COPD). However, the cellular mechanisms driving collagen remodeling and the functional implications of this process in the pathophysiology of pulmonary diseases remain poorly understood.
Methods: To address this question, we employed ; mice with specific depletion of Lyve-1 macrophages and assessed the content, types and organization of collagen in lung compartments at steady state and after chronic exposure to cigarette smoke (CS).
Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity.
View Article and Find Full Text PDFIndoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest.
View Article and Find Full Text PDFMatrix Biol
January 2025
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany. Electronic address:
Rapid progress has been made in the exciting field of secretome research in health and disease. The tumor secretome, which is a significant proportion of the tumor proteome, is secreted into the extracellular space to promote intercellular communication and thus tumor progression. Among the many molecules of the secretome, integrins and matrix metalloproteinase 14 (MMP14) stand out as the interplay of adhesion and proteolysis drives invasion.
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