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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.
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.
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.
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.
Lysine methyltransferases are well-known regulators of transcription through their methylation of histone lysine residues. Now high-throughput peptide arrays reveal non-histone substrates of G9a/KMT3C, which was previously known as a euchromatic histone H3K9-specific methyltransferase.
The search for new antimalarial strategies takes a step forward with the discovery of a small parasitocidal molecule that inhibits a calcium-dependent protein kinase and may thereby interfere with parasite motility.
A new pharmacological inhibitor of the Cdc7 protein kinase can block replication initiation without activating the replication checkpoint, thus validating replication initiation as a new target class for cancer cell chemotherapy.
Crosstalk between histone modifications plays an important role in transcriptional regulation. In a recent study, an elegant chemical synthesis approach has been used to study the intricate relationship between two modifications associated with active transcription.
Biosynthesis of essential hormones is often complex and redundant. Two independent genetic screens have converged to support a previously conjectured auxin biosynthetic pathway that is responsible for providing auxin during plant development and in response to environmental cues.
Engineering protease specificity has been a long sought research goal. New findings on OmpT, an outer membrane protease from Escherichia coli, reveal the remarkable success of a simple strategy.
DNA is the blueprint for life; it enables nature to pass on information from one DNA strand to the other, create mRNA with high accuracy and make proteins with absolute control over the sequence of the amino acid building blocks. A new paper now adds another templating function to the list: the programmed construction of synthetic polymers.
Enzymatic hydrolysis of β-mannosides was predicted to occur via an unusual boat transition state conformation. Structural and biochemical studies on transition state mimics of a retaining β-mannosidase now provide evidence for the predicted B2,5 transition state conformation.
