Volume 4 Issue 7, July 2008

New electrophilic reagents for activity-based protein profiling (ABPP) can discriminate between nucleophilic amino acids, such as cysteine, that are in different protein microenvironments. These reagents extend the reach of ABPP beyond serine proteases and other proteins with hyperreactive nucleophiles.

Leucascandrolide A and neopeltolide are structurally related natural products with potent growth inhibitory activity. The synthesis of a designed analog of leucascandrolide A and its evaluation in a yeast haploinsufficiency screen has revealed the cytochrome bc₁ complex as a molecular target of these compounds.

The NMR structures of three intermediates bound to the pyridoxal-synthesizing enzyme Pdx1 illuminate its complex catalytic cycle. The success of this approach with a high-molecular-weight protein should encourage further applications of NMR techniques for characterizing enzyme reaction pathways.

The zebrafish has provided insights into the mechanisms of vertebrate development, in large part due to its amenability to optical imaging. While fluorescent proteins and other genetically encoded reporters are valuable imaging tools, synthetic probes can reveal dynamical processes such as glycan biosynthesis that are undetectable by conventional methods.

The significance of hydrogen bonds in protein structure was recognized as early as 1936 by Mirsky and Pauling, and the importance of hydrogen bonds in water-soluble proteins has since been studied extensively. Now a new paper takes an important step forward in characterizing the energetic significance of hydrogen bonds in membrane-soluble proteins.