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Background: RNA splicing is both ubiquitous and essential for the maturation of precursor mRNA molecules in eukaryotes. The process of trans-splicing involves the transfer of a short spliced leader (SL) RNA sequence to a consensus acceptor site on a separate pre-mRNA transcript. In Caenorhabditis elegans, a majority of pre-mRNA transcripts receive the 22-nucleotide SL from the SL1 RNA. Very little...
Background: Spo0F, a phosphotransferase containing an aspartyl pocket, is involved in the signaling pathway (phosphorelay) controlling sporulation in Bacillus subtilis. It belongs to the superfamily of bacterial response regulatory proteins, which are activated upon phosphorylation of an invariant aspartate residue. This phosphorylation is carried out in a divalent cation dependent reaction catalyzed...
The structure of the Nef-SH3 domain complex reveals how an SH3 domain can more effectively 'read' its linear proline-rich recognition element when it is presented within the context of a folded protein.
The crystal structure of T7 DNA ligase complexed with ATP illuminates the mechanism of covalent catalysis by a superfamily of nucleotidyl transferases that includes the ATP-dependent polynucleotide ligases and the GTP-dependent mRNA capping enzymes.
Background: The regulation of milk lactose biosynthesis is highly dependent on the action of a specifier protein, α-lactalbumin (LA). Together with a glycosyltransferase, LA forms the enzyme complex lactose synthase. LA promotes the binding of glucose to the complex and facilitates the biosynthesis of lactose. To gain further insight into the molecular basis of LA function in lactose synthase we have...
Background: Cholera toxin from Vibrio cholerae and the type I heat-labile enterotoxins (LT-Is) from Escherichia coli are oligomeric proteins with AB 5 structures. The type II heat-labile enterotoxins (LT-IIs) from E. coli are structurally similar to, but antigenically distinct from, the type I enterotoxins. The A subunits of type I and type II enterotoxins are homologous and activate adenylate...
Background: Transaldolase is one of the enzymes in the non-oxidative branch of the pentose phosphate pathway. It transfers a C3 ketol fragment from a ketose donor to an aldose acceptor. Transaldolase, together with transketolase, creates a reversible link between the pentose phosphate pathway and glycolysis. The enzyme is of considerable interest as a catalyst in stereospecific organic synthesis and...
Rotation of a DNA nucleotide out of the double helix and into a protein binding pocket ('base flipping') was first observed in the structure of a DNA methyltransferase. There is now evidence that a variety of proteins use base flipping in their interactions with DNA. Though the mechanism for base flipping is still unclear, we propose a three-step pathway: recognizing the target site and increasing...
Background: The Src family of tyrosine kinases is involved in the propagation of intracellular signals from many transmembrane receptors. Each member of the family contains two domains that regulate interactions with other molecules, one of which is the Src homology 3 (SH3) domain. Although structures have previously been determined for SH3 domains, and ideas about peptide-binding modes have been...
Focal adhesions provide a useful model for studying cell/extracellular matrix interactions and the subsequent cytoskeletal reorganization. Recent advances have suggested potential mechanisms by which cells may regulate focal adhesion assembly following integrin-mediated cell adhesion.
Background: Human thioredoxin reduces the disulfide bonds of numerous proteins in vitro, and can activate transcription factors such as NFκB in vivo. Thioredoxin can also act as a growth factor, and is overexpressed and secreted in certain tumor cells.Results Crystal structures were determined for reduced and oxidized wild type human thioredoxin (at 1.7 and 2.1 a nominal resolution, respectively),...
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