title: 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.affiliation: Molecular Structural Biology Laboratory, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4310, USA.
authors.forename: Y X
authors.initials: YX
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Neamati
authors.forename: J
authors.initials: J
authors.lastname: Jacob
authors.forename: I
authors.initials: I
authors.lastname: Palmer
authors.forename: S J
authors.initials: SJ
authors.lastname: Stahl
authors.forename: J D
authors.initials: JD
authors.lastname: Kaufman
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: H E
authors.initials: HE
authors.lastname: Winslow
authors.forename: Y
authors.initials: Y
authors.lastname: Pommier
authors.forename: P T
authors.initials: PT
authors.lastname: Wingfield
authors.forename: S
authors.initials: S
authors.lastname: Lee-Huang
authors.forename: A
authors.initials: A
authors.lastname: Bax
authors.forename: D A
authors.initials: DA
authors.lastname: Torchia
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D019757:Carbon-Oxygen Lyases / Q000378:metabolism; D002413:Cations, Divalent; D045647:DNA Glycosylases; D004279:DNA, Viral / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D016325:HIV Long Terminal Repeat; D015497:HIV-1; D006801:Humans; D008670:Metals; D008958:Models, Molecular; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011687:Purines / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D054790:Ribosome Inactivating Proteins, Type 2; D012996:Solutions
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D002413:Cations, Divalent; D004279:DNA, Viral; C066347:MAP30 protein, Momordica charantia; D008670:Metals; D010940:Plant Proteins; D011687:Purines; D011993:Recombinant Fusion Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012996:Solutions; D043223:Deoxyribonuclease IV (Phage T4-Induced); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase