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The level of an individual protein in cells treated with combinations of drugs is best explained by simple linear superposition of the protein levels in response to single drugs. This finding may facilitate rational design of higher order drug combinations.
The buildup of toxic intermediates during lignocellulose pretreatment limits the utility of this abundant biomass for biofuel production. A recent study on the degradation pathways of two of the most hazardous toxins, furfural and HMF, now paves the way for mechanism-based enhancements of biodetoxification efficiency.
NMR-measured order parameters of methyl groups can be used to quantify the entropy of protein conformational change associated with calmodulin–peptide ligand interactions. This conformational entropy is a major contributor to the affinity of calmodulin interactions and can now be determined experimentally on a per-atom basis.
A new NMR method—requiring only milligram quantities of substrates—uses isotopically labeled neighbor atoms to directly and continuously report on KIEs at the reaction center. Application of the methodology defines a reaction coordinate for sialidase hydrolysis.
Reversible palmitoylation controls the localization and signaling of Ras. Development of a potent and specific small molecule inhibitor of the thioesterase APT1 reveals that this enzyme depalmitoylates Ras in cells. Inhibition of APT1 led to redistribution and altered activity of HRas, NRas and an oncogenic mutant Ras.
O-polysaccharide is a major constituent of the bacterial cell wall, yet little mechanistic information is known about its biosynthesis. A reconstruction of this pathway using defined substrates now demonstrates the basis for sugar polymerization and length modulation.
Expression of vancomycin resistance genes is known to be controlled by the two-component regulatory system VanRS, but the identity of the VanS receptor ligand has been controversial. Synthesis of a vancomycin photoaffinity probe has now revealed that vancomycin directly binds VanS to induce the expression of resistance genes.
NMR-measured order parameters of methyl groups can be used to quantitate the entropy of protein conformational change associated with calmodulin-peptide ligand interactions. This conformational entropy is a major contributor to the affinity of calmodulin interactions.
Glycosyltransferases transfer sugars from a donor to an acceptor, with current inhibitors directly competing with these substrates. Modification of the donor reveals a new mode of allosteric inhibition in which a bulky substituent prevents conformational changes and thus enzyme activation.
A membrane-permeant caged derivative of PtdIns(3)P induces EEA1-dependent endosomal fusion upon photoactivation in vivo, potentially with a time course close to that of the native process.
Functionally coupled motions between the voltage-sensing and the phosphatidylinositol phosphatase domains of the sea squirt protein Ci-VSP are mediated by PtdIns(4,5)P2 binding to the segment linking these domains, as shown by electrophysiology and voltage clamp fluorometry.
The detailed characterization of endogenous proteins and use of non-natural amino acid engineering allows the identification and structural and functional analysis of a post-translational modification in regulating ligand binding and enzyme activity.