Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions.

Abstract	We present the solution structure of MAP30, a plant protein with anti-HIV and anti-tumor activities. Structural analysis and subsequent biochemical assays lead to several novel discoveries. First, MAP30 acts like a DNA glycosylase/apurinic (ap) lyase, an additional activity distinct from its known RNA N-glycosidase activity toward the 28S rRNA. Glycosylase/ap lyase activity explains MAP30's apparent inhibition of the HIV-1 integrase, MAP30's ability to irreversibly relax supercoiled DNA, and may be an alternative cytotoxic pathway that contributes to MAP30's anti-HIV/anti-tumor activities. Second, two distinct, but contiguous, subsites are responsible for MAP30's glycosylase/ap lyase activity. Third, Mn2+ and Zn2+ interact with negatively charged surfaces next to the catalytic sites, facilitating DNA substrate binding instead of directly participating in catalysis.
Authors	Y X Wang, N Neamati, J Jacob, I Palmer, S J Stahl, J D Kaufman, P L Huang, P L Huang, H E Winslow, Y Pommier, P T Wingfield, S Lee-Huang, A Bax, D A Torchia
Journal	Cell (Cell) Vol. 99 Issue 4 Pg. 433-42 (Nov 12 1999) ISSN: 0092-8674 [Print] United States
PMID	10571185 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Anti-HIV Agents Antineoplastic Agents Cations, Divalent DNA, Viral MAP30 protein, Momordica charantia Metals Plant Proteins Purines Recombinant Fusion Proteins Ribosome Inactivating Proteins, Type 2 Solutions Deoxyribonuclease IV (Phage T4-Induced) DNA Glycosylases N-Glycosyl Hydrolases Carbon-Oxygen Lyases DNA-(Apurinic or Apyrimidinic Site) Lyase
Topics	Anti-HIV Agents (chemistry, metabolism) Antineoplastic Agents (chemistry, metabolism) Binding Sites Carbon-Oxygen Lyases (metabolism) Cations, Divalent DNA Glycosylases DNA, Viral (metabolism) DNA-(Apurinic or Apyrimidinic Site) Lyase Deoxyribonuclease IV (Phage T4-Induced) HIV Long Terminal Repeat HIV-1 Humans Metals Models, Molecular N-Glycosyl Hydrolases (metabolism) Nuclear Magnetic Resonance, Biomolecular Plant Proteins (chemistry, metabolism, physiology) Protein Conformation Protein Structure, Secondary Purines (metabolism) Recombinant Fusion Proteins (chemistry, metabolism, physiology) Ribosome Inactivating Proteins, Type 2 Solutions

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