Conserved Helix-Flanking Prolines Modulate Intrinsically Disordered Protein:Target Affinity by Altering the Lifetime of the Bound Complex.

Appropriate integration of cellular signals requires a delicate balance of ligand-target binding affinities. Increasing the level of residual structure in intrinsically disordered proteins (IDPs), which are overrepresented in these cellular processes, has been shown previously to enhance binding affinities and alter cellular function. Conserved proline residues are commonly found flanking regions of IDPs that become helical upon interacting with a partner protein. Here, we mutate these helix-flanking prolines in p53 and MLL and find opposite effects on binding affinity upon an increase in free IDP helicity. In both cases, changes in affinity were due to alterations in dissociation, not association, rate constants, which is inconsistent with conformational selection mechanisms. We conclude that, contrary to previous suggestions, helix-flanking prolines do not regulate affinity by modulating the rate of complex formation. Instead, they influence binding affinities by controlling the lifetime of the bound complex

Augmented gut hormone response to feeding in older adults exhibiting low appetite

This manuscript has been made open access under a Creative Commons Attribution (CC BY) licence under the terms of the University of Aberdeen Research Publications Policy. https://creativecommons.org/licenses/by/4.0/Peer reviewe

Anodic deposition of a robust iridium-based water-oxidation catalyst from organometallic precursors

Artificial photosynthesis, modeled on natural light-driven oxidation of water in Photosystem II, holds promise as a sustainable source of reducing equivalents for producing fuels. Few robust water-oxidation catalysts capable of mediating this difficult four-electron, four-proton reaction have yet been described. We report a new method for generating an amorphous electrodeposited material, principally consisting of iridium and oxygen, which is a robust and long-lived catalyst for water oxidation, when driven electrochemically. The catalyst material is generated by a simple anodic deposition from Cp*Ir aqua or hydroxo complexes in aqueous solution. This work suggests that organometallic precursors may be useful in electrodeposition of inorganic heterogeneous catalysts

A full set of iridium(iv) pyridine-alkoxide stereoisomers: highly geometry-dependent redox properties

© The Royal Society of Chemistry. We introduce and characterize the complete set of possible isomers of IrIV(pyalk)2Cl2 (pyalk = 2-(pyridin-2-yl)propan-2-oate), providing valuable insights on the properties of Ir(iv) species. The pyridine alkoxide ligand strongly stabilizes high oxidation states, essential to accessing the catalytically relevant Ir(iv) state, and results in robust complexes that can be handled under ambient conditions, even permitting chromatographic separation. The redox properties are isomer-dependent, spanning a 300 mV range, rationalized with ligand-field theory and DFT calculations. The reported complexes exhibit very high kinetic inertness against isomerization, despite highly disparate predicted thermodynamic stabilities, presenting a unique opportunity to study all five possible isomeric complexes with the same ligand set

N,N,O Pincer Ligand with a Deprotonatable Site That Promotes Redox‐Leveling, High Mn Oxidation States, and a Mn2O2 Dimer Competent for Catalytic Oxygen Evolution

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149230/1/ejic201801343.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149230/2/ejic201801343_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149230/3/ejic201801343-sup-0001-SupMat.pd