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Article
Open AccessProtein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing
If and how proteasomes catalyze not only peptide hydrolysis but also peptide splicing is an open question that has divided the scientific community. The debate has so far been based on immunopeptidomics, in vi...
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Article
Open AccessMultiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design
Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for preventing future COVID outbreaks. The SARS-CoV-2 main protease (Mpro), a cysteine protease with essential functions in vi...
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Article
Ground-state destabilization by electrostatic repulsion is not a driving force in orotidine-5′-monophosphate decarboxylase catalysis
The origins of enzyme catalysis have been attributed to both transition-state stabilization as well as ground-state destabilization of the substrate. For the latter paradigm, the enzyme orotidine-5′-monophosph...
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Chapter
Fatty Acid Synthase: Structure, Function, and Regulation
Fatty acid (FA) biosynthesis plays a central role in the metabolism of living cells as building blocks of biological membranes, energy reserves of the cell, and precursors to second messenger molecules. In kee...
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Article
Atomic-resolution protein structure determination by cryo-EM
Single-particle electron cryo-microscopy (cryo-EM) is a powerful method for solving the three-dimensional structures of biological macromolecules. The technological development of transmission electron microsc...
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Article
Cryo-EM in drug discovery: achievements, limitations and prospects
Recent technological advances with cryo-electron microscopy (cryo-EM) — a biophysical technique that can be used to determine the structure of biological macromolecules and assemblies — have raised hopes that ...
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Article
Open AccessLong-range allosteric regulation of the human 26S proteasome by 20S proteasome-targeting cancer drugs
The proteasome holoenzyme is the major non-lysosomal protease; its proteolytic activity is essential for cellular homeostasis. Thus, it is an attractive target for the development of chemotherapeutics. While t...
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Article
ProteoPlex: stability optimization of macromolecular complexes by sparse-matrix screening of chemical space
ProteoPlex optimizes buffer conditions for the isolation and purification of macromolecular complexes. The concurrent complex stabilization is beneficial for structure determination using X-ray crystallography...