Efficient inhibition of hepatitis B virus replication in vivo, using polyethylene glycol-modified adenovirus vectors.

Achieving safe delivery of anti-hepatitis B virus (HBV) RNA interference (RNAi) effectors is an important objective of this gene-silencing technology. Adenoviruses (Ads) have a natural tropism for the liver after systemic administration, and are useful for delivery of expressed anti-HBV RNAi sequences. However, a drawback of Ad vectors is diminished efficacy and toxicity that results from stimulation of innate and adaptive immunity.

Tetratricopeptide repeat motif-mediated Hsc70-mSTI1 interaction. Molecular characterization of the critical contacts for successful binding and specificity.

Murine stress-inducible protein 1 (mSTI1) is a co-chaperone that is homologous with the human Hsp70/Hsp90-organizing protein (Hop). Guided by Hop structural data and sequence alignment analyses, we have used site-directed mutagenesis, co-precipitation assays, circular dichroism spectroscopy, steady-state fluorescence, and surface plasmon resonance spectroscopy to both qualitatively and quantitatively characterize the contacts necessary for the N-terminal tetratricopeptide repeat domain (TPR1) of mSTI1 to bind to heat shock cognate protein 70 (Hsc70) and to discriminate between Hsc70 and Hsp90. We have shown that substitutions in the first TPR motif of Lys(8) or Asn(12) did not affect binding of mSTI1 to Hsc70, whereas double substitution of these residues abrogated binding.

Molecular recognition at the dimer interface of a class mu glutathione transferase: role of a hydrophobic interaction motif in dimer stability and protein function.

Cytosolic glutathione (GSH) transferases (GSTs) exist as stable homo- and heterodimers. Interactions at the subunit interface serve an important role in stabilizing the subunit tertiary structures of all GSH transferases. In addition, the dimer is required to maintain functional conformations at the active site on each subunit and the nonsubstrate ligand binding site at the dimer interface [Dirr, H.

Impact of domain interchange on conformational stability and equilibrium folding of chimeric class micro glutathione transferases.

Rat micro class glutathione transferases M1-1 and M2-2 are homodimers that share a 78% sequence identity but display differences in stability. M1-1 is more stable at the secondary and tertiary structural levels, whereas its quaternary structure is less stable. Each subunit in these proteins consists of two structurally distinct domains with intersubunit contacts occurring between domain 1 of one subunit and domain 2 of the other subunit.

Thermodynamics of the ligandin function of human class Alpha glutathione transferase A1-1: energetics of organic anion ligand binding.

In addition to their catalytic functions, cytosolic glutathioneS-transferases (GSTs) are a major reserve of high-capacity binding proteins for a large variety of physiological and exogenous non-substrate compounds. This ligandin function has implicated GSTs in numerous ligand-uptake, -transport and -storage processes. The binding of non-substrate ligands to GSTs can inhibit catalysis.