Volume 2 Issue 4, April 2006

Iron-sulfur clusters have critical roles in proteins from diverse organisms and in a broad range of biological processes. Recent discoveries raise exciting challenges for future research by bioinorganic chemists and chemical biologists.

GPR30, a G-protein coupled receptor, is a recent addition to the family of receptors that bind to estrogens and antiestrogens. A new, selective compound for GPR30 has been developed to dissect the role of GPR30 in estrogen signaling.

Eukaryotic initiation factor (eIF) 4A plays an essential role in translation initiation on most eukaryotic mRNAs by unwinding their secondary structure to permit ribosomal attachment and scanning. The natural product hippuristanol selectively inhibited eIF4A- and eIF4A-dependent modes of translation initiation.

Square-planar, four-coordinate metal complexes strip peptides from the binding site of MHC class II molecules. Removal of peptides derived from self-antigens could prevent class II–dependent activation of self-reactive T cells in autoimmune diseases such as rheumatoid arthritis.

The enzyme γ-humulene synthase normally generates a mixture of more than 50 sesquiterpene products from a single substrate. Targeted evolution allowed the design of new mutants with greatly enhanced product specificity. The results provide a model for the divergent evolution of enzyme specificity from ancestral proteins of promiscuous function.

The hypothesis of ubiquitous fluctuations in gene expression has spurred the development of general methods for tracking temporal changes in protein concentrations in individual cells. The determination of protein levels with single-molecule sensitivity represents a significant advancement in the monitoring of cellular behavior that is driven by gene expression.

The modified tRNA base 2-thiouridine is required for many steps in translation. Surprisingly, the biosynthesis of this simple derivative requires a minimum of four sulfur transfer reactions involving seven proteins.