Molecules, 2020 In recent years, new drug discovery approaches based on novel pharmacological concepts have emerged. Allosteric modulators, for example, target receptors at sites other than the orthosteric binding sites and can modulate agonist-mediated activation ...
Víctor Fernández-Dueñas +6 more
doaj +1 more source
Conformational spread as a mechanism for cooperativity in the bacterial flagellar switch [PDF]
, 2010 The bacterial flagellar switch that controls the direction of flagellar rotation during chemotaxis has a highly cooperative response. This has previously been understood in terms of the classic two-state, concerted model of allosteric regulation.
F. Bai +29 more
core +3 more sources
Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity
eLife, 2020 Engineered allosteric regulation of protein activity provides significant advantages for the development of robust and broadly applicable tools. However, the application of allosteric switches in optogenetics has been scarce and suffers from critical ...
Mark Shaaya +14 more
doaj +1 more source
Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation. [PDF]
, 2019 PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications.
Chen, Tsan-Jan +11 more
core +3 more sources
Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I [PDF]
, 2012 Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity.
Badura, Susanne +8 more
core +1 more source
Frontiers in Bioengineering and Biotechnology, 2015 Modeling metabolism is fundamental for cell factory design. Central carbon metabolism (CCM) is particularly important as it provides the energy and precursors for other biological processes.
Daniel eMachado +2 more
doaj +1 more source
Structurally distributed surface sites tune allosteric regulation [PDF]
eLife, 2021 Our ability to rationally optimize allosteric regulation is limited by incomplete knowledge of the mutations that tune allostery. Are these mutations few or abundant, structurally localized or distributed? To examine this, we conducted saturation mutagenesis of a synthetic allosteric switch in which Dihydrofolate reductase (DHFR ...
James W. McCormick +4 more
openaire +3 more sources
Rational engineering of enzyme allosteric regulation through sequence evolution analysis.
PLoS Computational Biology, 2012 Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D) structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an ...
Jae-Seong Yang +4 more
doaj +1 more source
Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures
Nature Communications, 2022 DNA aptamers can activate insulin receptor as selective agonists or positive allosteric modulators. Here, authors determine structures of the insulin receptor bound to aptamers and provide a basis for the selective activation or allosteric regulation of ...
Junhong Kim +8 more
doaj +1 more source
The calcium-sensing receptor as a regulator of cellular fate in normal and pathological conditions [PDF]
, 2013 The calcium-sensing receptor (CaSR) belongs to the evolutionarily conserved family of plasma membrane G protein-coupled receptors (GPCRs). Early studies identified an essential role for the CaSR in systemic calcium homeostasis through its ability to ...
Benoit, Yves +3 more
core +1 more source