A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase - Structural and modeling insight into its functions

Hui Guang Li, Philip L. Huang, Dawei Zhang, Yongtao Sun, Hao Chia Chen, John Zhang, Paul L. Huang, Xiang Peng Kong, Sylvia Lee-Huang

Research output: Contribution to journalArticlepeer-review

Abstract

We report here the high-resolution atomic structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5′ overhanging adenosine ends, such as the 3′-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5′ overhanging adenosine of the 3′-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third, GAP31 also removes the 5′-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA.

Original languageEnglish (US)
Pages (from-to)340-345
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • AIDS
  • Adenosine glycosidase
  • Anti-tumor
  • Antiviral
  • HIV-1
  • Plant protein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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