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All over or overall - Do we understand allostery?
Curr Opin Struct Biol. 2023 Oct 26;83:102724. doi: 10.1016/j.sbi.2023.102724. Online ahead of print.ABSTRACTAllostery is probably the most important concept in the regulation of cellular processes. Models to explain allostery are plenty. Each sheds light on different aspects but their entirety conveys an ambiguous feeling of comprehension and disappointment. Here, I discuss the most popular allostery models, their roots, similarities, and limitations. All of them are thermodynamic models. Naturally this bears a certain degree of redundancy, which forms the center of this review. After sixty years, many questions remain una...
Source: Current Opinion in Structural Biology - October 28, 2023 Category: Biology Authors: Hagen Hofmann Source Type: research

Cell phenotypes can be predicted from propensities of protein conformations
Curr Opin Struct Biol. 2023 Oct 21;83:102722. doi: 10.1016/j.sbi.2023.102722. Online ahead of print.ABSTRACTProteins exist as dynamic conformational ensembles. Here we suggest that the propensities of the conformations can be predictors of cell function. The conformational states that the molecules preferentially visit can be viewed as phenotypic determinants, and their mutations work by altering the relative propensities, thus the cell phenotype. Our examples include (i) inactive state variants harboring cancer driver mutations that present active state-like conformational features, as in K-Ras4BG12V compared to other K-R...
Source: Current Opinion in Structural Biology - October 23, 2023 Category: Biology Authors: Ruth Nussinov Yonglan Liu Wengang Zhang Hyunbum Jang Source Type: research

The new epoch of structural insights into radical SAM enzymology
Curr Opin Struct Biol. 2023 Oct 18;83:102720. doi: 10.1016/j.sbi.2023.102720. Online ahead of print.ABSTRACTThe Radical SAM (RS) superfamily of enzymes catalyzes a wide array of enzymatic reactions. The majority of these enzymes employ an electron from a reduced [4Fe-4S]+1 cluster to facilitate the reductive cleavage of S-adenosyl-l-methionine, thereby producing a highly reactive 5'-deoxyadenosyl radical (5'-dA⋅) and l-methionine. Typically, RS enzymes use this 5'-dA⋅ to extract a hydrogen atom from the target substrate, starting the cascade of an expansive and impressive variety of chemical transformations. While a gr...
Source: Current Opinion in Structural Biology - October 20, 2023 Category: Biology Authors: Jake Lachowicz James Lee Alia Sagatova Kristen Jew Tyler L Grove Source Type: research

Recent developments in catalysis and inhibition of the Jumonji histone demethylases
Curr Opin Struct Biol. 2023 Oct 11;83:102707. doi: 10.1016/j.sbi.2023.102707. Online ahead of print.ABSTRACTHistone methylation, one of the most common histone modifications, has fundamental roles in regulating chromatin-based processes. Jumonji histone lysine demethylases (JMJC KDMs) influence regulation of gene transcription through both their demethylation and chromatin scaffolding functions. It has recently been demonstrated that dysregulation of JMJC KDMs contributes to pathogenesis and progression of several diseases, including cancer. These observations have led to an increased interest in modulation of enzymes that...
Source: Current Opinion in Structural Biology - October 13, 2023 Category: Biology Authors: Letitia Sarah Danica Galoni ć Fujimori Source Type: research