Reviews & Analysis

One of the primary functions of the Golgi apparatus is the assembly of glycans on macromolecules destined for secretion or the plasma membrane. A recent study describes the first step toward an artificial Golgi, based on a microfluidic chip and magnetic nanoparticles.

A small-molecule inhibitor of the obligate dimeric protease of human Kaposi's sarcoma–associated herpesvirus was identified. The agent functions by a 'monomer trap' mechanism in which the compound binds to a partially unfolded monomer and disrupts the formation of the enzymatically active protease dimer.

A cocrystal structure of the enzyme that synthesizes selenocysteine reveals the elegantly simple recognition mechanism for the tRNA molecule for this '21^st amino acid'. The structure resolves some mechanistic questions and allows for comparison of the tRNA-dependent synthesis of cysteine and selenocysteine.

Screening a library of expressed cyclic peptides identified clones that reverse the cytotoxicity of α-synuclein in yeast and Caenorhabditis elegans. The results suggest a new approach for intervention in Parkinson's disease, and perhaps a druggable target.

The parallel determination of more than 100 absolute intracellular metabolite concentrations by isotope-labeled HPLC-MS allowed a comprehensive analysis of the cellular state, its metabolic capacities and modes of regulation. Among other findings, it became obvious that for most enzymes the concentrations were above the K_m values, which indicates a trend toward saturation of most enzyme active sites.

New software to browse chemical space, with structures organized by rings, will enable chemical insight.

Random mutations usually destabilize protein tertiary structure. Overexpression of the chaperonin GroEL/GroES protects evolving proteins from the destabilizing effects of adaptive mutations and improves the quantity and quality of enzyme variants with modified function.

The 2009 ESBOC meeting covered advances in synthesis, biosynthesis and biological mechanisms of vitamins and cofactors. Recent exciting developments in the field include the development of 'green' chemistry for manufacture of vitamins, the discovery that some vitamins act directly to regulate gene expression via riboswitches, and initial attempts to exploit the potential of vitamin analogs as therapeutic drugs.

Microorganisms are a major source of new therapeutics. However, the discovery and sustainable production of these compounds are often hampered owing to limited access to biosynthetic genes or products. Recent studies provide new approaches for targeting biosynthesis genes in the metagenome of complex microbial assemblages and for inducing the expression of otherwise silent biosynthesis genes.

A new methodology combining small molecules and phage-displayed peptides enables the isolation of chemically modified bicyclic peptides capable of high-affinity recognition of target proteins.

Westheimer's classical proposal that the decreased pK_a of Lys115 in the active site of acetoacetate decarboxylase is the result of its unfavorable electrostatic juxtaposition with Lys116 has been evaluated by X-ray crystallography. The long-awaited structure reveals that Lys115 is positioned in a hydrophobic pocket that lowers its pK_a.

Synthetic agonists of sphingosine-1-phosphate receptor subtype 1 are able to generate long-term signaling that persists for hours after ligand-induced receptor internalization. These signals are independent of agonist potency, can be reversed after receptor internalization by specific antagonists, and show a distinct acyl-chain-length structure-activity relationship.

Peptide bond formation is catalyzed from stable aminoacyl-tRNA intermediates by several specialized proteins. A new set of these enzymes forming cyclodipeptides present the first usage of tRNAs in secondary metabolism.