Michael Laskowski Jr. (1930-2004) was a pioneer in the field of Standard mechanism serine proteinase inhibitors. He made numerous important contributions in the field. This article highlights some of his most important contributions such as the discovery of the reactive site in serine proteinase inhibitors, the proposal of the Standard mechanism of inhibition, and the sequence to reactivity algorithm for the Kazal family of inhibitors.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2174/0929866054395347 | DOI Listing |
Trends Chem
November 2024
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States.
BURP domain peptide cyclases, or BpCs (an abbreviation we recommend in this opinion), are an emerging class of copper enzymes which catalyze the oxidative macrocyclization of peptides in plants. A close examination of their novel protein fold, along with the unique dicopper active site that meticulously controls crosslinking within peptides, highlights how nature exploits intricate mechanistic strategies to achieve diverse functionalities. Here, we summarize recent discoveries regarding the sequence, structure, function, and proposed chemistry of BpCs.
View Article and Find Full Text PDFAnn Neurol
January 2025
Neuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia", Catanzaro, Italy.
Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).
View Article and Find Full Text PDFBMC Neurosci
January 2025
Department of Operative Dentistry and Periodontology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).
View Article and Find Full Text PDFAcc Chem Res
January 2025
Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany.
ConspectusSkeletal editing, which involves adding, deleting, or substituting single or multiple atoms within ring systems, has emerged as a transformative approach in modern synthetic chemistry. This innovative strategy addresses the ever-present demand for developing new drugs and advanced materials by enabling precise modifications of molecular frameworks without disrupting essential functional complexities. Ideally performed at late stages of synthesis, skeletal editing minimizes the need for the cost- and labor-intensive processes often associated with synthesis, thus accelerating the discovery and optimization of complex molecular architectures.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Misregulation of protein-protein interactions (PPIs) underlies many diseases; hence, molecules that stabilize PPIs, known as molecular glues, are promising drug candidates. Identification of novel molecular glues is highly challenging among others because classical biochemical assays in dilute aqueous conditions have limitations for evaluating weak PPIs and their stabilization by molecular glues. This hampers the systematic discovery and evaluation of molecular glues.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!