3KTZ

Structure of GAP31

Summary for 3KTZ

• Entry DOI: 10.2210/pdb3ktz/pdb
• Related: 3KU0
• Descriptor: Ribosome-inactivating protein gelonin, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: plant seeds, glycosidase, disulfide bond, glycoprotein, hydrolase, plant defense, protein synthesis inhibitor, toxin
• Biological source: Gelonium multiflorum (Euphorbiaceae himalaya)
• Total number of polymer chains: 2
• Total formula weight: 56860.78

Authors

Kong, X.-P. (deposition date: 2009-11-26, release date: 2010-01-26, Last modification date: 2020-07-29)

Primary citation

Li, H.G.,Huang, P.L.,Zhang, D.,Sun, Y.,Chen, H.C.,Zhang, J.,Huang, P.L.,Kong, X.P.,Lee-Huang, S.
A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase--structural and modeling insight into its functions.
Biochem.Biophys.Res.Commun., 391:340-345, 2010

PubMed 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.

PubMed: 19913503
DOI: 10.1016/j.bbrc.2009.11.060

Experimental method

X-RAY DIFFRACTION (1.6 Å)