Search results for "allostery"
showing 5 items of 5 documents
Recent advances in computational design of potent aromatase inhibitors: open-eye on endocrine-resistant breast cancers.
2019
Introduction: The vast majority of breast cancers (BC) are estrogen receptor positive (ER+). The most effective treatments to fight this BC type rely on estrogen deprivation therapy, by inhibiting the aromatase enzyme, which performs estrogen biosynthesis, or on blocking the estrogens signaling path via modulating/degrading the estrogen's specific nuclear receptor (estrogen receptor-?, ER?). While being effective at early disease stage, patients treated with aromatase inhibitors (AIs) may acquire resistance and often relapse after prolonged therapies. Areas covered: In this compendium, after an overview of the historical development of the AIs currently in clinical use, and of the computati…
A lipid transfer protein binds to a receptor involved in the control of plant defence responses
2001
AbstractLipid transfer proteins (LTPs) and elicitins are both able to load and transfer lipidic molecules and share some structural and functional properties. While elicitins are known as elicitors of plant defence mechanisms, the biological function of LTP is still an enigma. We show that a wheat LTP1 binds with high affinity sites. Binding and in vivo competition experiments point out that these binding sites are common to LTP1 and elicitins and confirm that they are the biological receptors of elicitins. A mathematical analysis suggests that these receptors could be represented by an allosteric model corresponding to an oligomeric structure with four identical subunits.
The Monod-Wyman-Changeux allosteric model accounts for the quaternary transition dynamics in wild type and a recombinant mutant human hemoglobin
2012
International audience; The acknowledged success of the Monod-Wyman-Changeux (MWC) allosteric model stems from its efficacy in accounting for the functional behavior of many complex proteins starting with hemoglobin (the paradigmatic case) and extending to channels and receptors. The kinetic aspects of the allosteric model, however, have been often neglected, with the exception of hemoglobin and a few other proteins where conformational relaxations can be triggered by a short and intense laser pulse, and monitored by time-resolved optical spectroscopy. Only recently the application of time-resolved wide-angle X-ray scattering (TR-WAXS), a direct structurally sensitive technique, unveiled th…
Unveiling the timescale of the R-T transition in human hemoglobin.
2010
Time-resolved wide-angle X-ray scattering, a recently developed technique allowing to probe global structural changes of proteins in solution, was used to investigate the kinetics of R-T quaternary transition in human hemoglobin and to systematically compare it to that obtained with time-resolved optical spectroscopy under nearly identical experimental conditions. Our data reveal that the main structural rearrangement associated with the R-T transition takes place approximately 2 mus after the photolysis of hemoglobin at room temperature and neutral pH. This finding suggests that the 20-mus step observed with time-resolved optical spectroscopy corresponds to a small and localized structural…
The Interconnecting Hairpin Extension "Arm": An Essential Allosteric Element of Phytochrome Activity
2023
In red-light sensing phytochromes, isomerization of the bilin chromophore triggers structural and dynamic changes across multiple domains, ultimately leading to control of the output module (OPM) activity. In between, a hairpin structure, "arm", extends from an interconnecting domain to the chromophore region. Here, by removing this protein segment in a bacteriophytochrome from Deinococcus radiodurans (DrBphP), we show that the arm is crucial for signal transduction. Crystallographic, spectroscopic, and biochemical data indicate that this variant maintains the properties of DrBphP in the resting state. Spectroscopic data also reveal that the armless systems maintain the ability to respond t…