Allison Walker

Harvard Medical School | HMS · Department of Biological Chemistry and Molecular Pharmacology

Research in natural products, the genetically encoded small molecules produced by organisms in an idiosyncratic fashion, deals with molecular structure, biosynthesis, and biological activity. Bioinformatics analyses of microbial genomes can successfully reveal the genetic instructions, biosynthetic gene clusters, that produce many natural products....

Significance The ribosome is a large, complex, and essential biomolecular machine. Despite its importance in all domains of life, the long-range interactions that regulate ribosome function are poorly understood. Here we report that statistical coupling analysis (SCA), a method previously only applied to proteins, can identify networks of coevolvin...

A twisted small-molecule synthesis Some molecules are easy to draw on paper, whereas others contain rings and contortions that require one to think in three dimensions. Reisberg et al. set out to synthesize the bicyclic small molecule tryptorubin A but found that their initial attempt produced a molecule with the right bonds but the wrong molecular...

Epidermal growth factor receptor (EGFR) interacts through its extracellular domain with seven different growth factors. These factors induce different structures within the cytoplasmic juxtamembrane (JM) segment of the dimeric receptor and propagate different growth factor-dependent signals to the cell interior. How this process occurs is unknown....

Fluorogenic dyes such as FlAsH and ReAsH are used widely to localize, monitor, and characterize proteins and their assemblies in live cells. These bis-arsenical dyes can become fluorescent when bound to a protein containing four proximal Cys thiols-a tetracysteine (Cys4) motif. Yet the mechanism by which bis-arsenicals become fluorescent upon bindi...

It has recently been reported that ribosomes from erythromycin-resistant Escherichia coli strains, when isolated in S30 extracts and incubated with chemically mis-acylated tRNA, can incorporate certain β-amino acids into full length DHFR in vitro. Here we report that wild-type E. coli EF-Tu and phenylalanyl-tRNA synthetase collaborate with these mu...

The selective recruitment of oligosaccharides, or even simple sugars, in water solvent is an unsolved molecular recognition problem. Structure-guided, electrostatic redesign led to a significant increase in the affinity of a β-peptide "borono-bundle" for simple sugars in neutral aqueous solution. The affinity for fructose (663 M(-1)) in water shoul...

Despite significant progress in the design of receptors and sensors for simple polyols and monosaccharides, few synthetic receptors discriminate among multiple saccharide units simultaneously, especially under physiological conditions. Described here is the three-dimensional structure of a supramolecular complex-a β-peptide bundle-designed for the...

The cell interior is a complex and demanding environment. An incredible variety of molecules jockey to identify the correct position – the specific interactions that promote biology, which are often hidden among countless unproductive options. Ensuring that the business of the cell is successful requires sophisticated mechanisms to impose temporal...