Volume 8 Issue 1, January 2001

Priming of DNA replication in eukaryotes is carried out by a heterotetrameric complex known as pol α–primase. The structure of the Pyrococcus furiosus RNA polymerase subunit of this complex shows that priming is carried out by unrelated proteins in archaea/eukarya and eubacteria, provides insights into the mechanism of action of a novel RNA polymerase, and raises new questions regarding the ancestry of priming and replication in the three domains of life.

Imidazole glycerol phosphate synthase (HisF) has been proposed to be the product of duplication of a gene encoding a (β/α)₄-half barrel followed by fusion to encode the complete (β/α)₈-barrel. In support of this evolutionary scenario, the N- and C-terminal (β/α)₄-half barrels of HisF* have been separately expressed and purified. Each assumes a stable, soluble homodimeric structure, but neither is catalytically active; when expressed together, a functional heterodimer is formed.

The structure of yeast Esa1 suggests that different families of histone acetyltransferases employ similar mechanisms of substrate binding and catalysis. Deletion studies used to optimize the protein for crystallization also emphasize the importance of Esa1 function within a larger, multiprotein HAT complex.

A conserved region of U6 small nuclear RNA has been implicated in binding an essential metal ion. Is this a glimpse of the spliceosome's catalytic core?

The first structural analysis of part of the spinal muscular atrophy (SMA)-causing 'survival of motor neurons' (SMN) protein reveals a structural similarity to the common spliceosomal small nuclear ribonucleoprotein (snRNP) Sm proteins. This observation gives clues to possible SMN roles in the cell, the loss of which may contribute to the pathogenesis of SMA.

An efficient bisubstrate inhibitor of insulin receptor tyrosine kinase has been created by connecting modules that target the ATP- and peptide-binding sites.