Volume 6 Issue 5, May 2010

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.

Bacteria resistant to glycopeptides such as vancomycin sense the drugs and escape killing by remodeling synthesis of the cell wall target. A photoaffinity probe shows that induction of resistance relies on direct drug recognition by a glycopeptide sensor.

Functionally coupled motions between the voltage-sensing and the phosphatidylinositol phosphatase domains of the sea squirt protein Ci-VSP is mediated by PI(4,5)P₂ binding to the intervening linker, shedding light on the function of an unusual voltage-sensing protein.

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.

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.

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.

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.

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.

Glycosylation can affect biological targets transiently and at low levels, making the development of diagnostic tools of critical importance. The application of a new series of antibodies raised against GlcNAc-modified substrates identifies a host of protein targets in normal and traumatized cells.

Elongation factor G (EF-G) is an essential GTPase involved in translation, but how the translocating ribosome activates EF-G remains an open question. Nucleotide functional group mutagenesis implicates A2660 of 23S rRNA as the trigger of GTPase hydrolysis by EF-G.

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.

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.

GlgE is identified as a maltosyltransferase that catalyzes the polymerization step in a previously undescribed pathway in Mycobacterium tuberculosis for converting trehalose to α-glucan. A combination of traditional and chemical genetic strategies suggest GlgE to be a viable therapeutic target.