Journal of Proteomics & Bioinformatics
Open Access

Seiichiro Ogawa

Publications

• Research Article
  Molecular Basis of Chemical Chaperone Effects of N-octyl-β-valienamine on Human β-glucosidase in Low/neutral pH Conditions
  Author(s): Hiroyuki Jo, Katsuyuki Yugi, Seiichiro Ogawa, Yoshiyuki Suzuki and Yasubumi Sakakibara Hiroyuki Jo, Katsuyuki Yugi, Seiichiro Ogawa, Yoshiyuki Suzuki and Yasubumi Sakakibara
  
  Chemical chaperone therapy is a strategy for restoring the activities of mutant lysosomal hydrolases. This therapy involves chemical compounds binding to the dysfunctional enzymes. The chemical chaperones for lysosomal hydrolases are anticipated to stabilize folding of target enzymes by binding at neutral pH and rescuing enzyme activities by dissociation in acidic conditions after transport to lysosome. However, the molecular basis describing the mechanism of action of chemical chaperones has not been analysed sufficiently. Here we present results derived from molecular dynamics simulations showing that the binding free energy between human ?-glucosidase and its known chemical chaperone, N-octyl-?-valienamine (NOV), is lower at pH 7 than at pH 5. This observation is consistent with the hypothetical activity of chemical chaperones. The pH conditions we.. View More»
  DOI: 10.4172/jpb.1000128

  Abstract PDF

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