High resolution X-ray structure and potent anti-HIV activity of recombinant dianthin antiviral protein.
Dianthin antiviral protein (DAP) is a naturally occurring antiviral protein from the leaves of carnation (Dianthus caryophyllus) capable of depurinating HIV-1 RNA and inhibiting HIV-1 replication in human peripheral blood mononuclear cells. Escherichia coli-derived recombinant DAP (rDAP, amino acids 1-254) was purified to homogeneity for structural and functional studies. In the following paper the X-ray crystal structure of rDAP as well as its complexes with cyclic AMP and adenyl-guanosine (ApG) as substrate analogs at 1.7 A resolution are reported. Molecular modeling studies of the interactions of DAP and the structurally similar pokeweed antiviral protein (PAP) with a single-stranded RNA heptamer predicted a more potent anti-HIV activity for rDAP due to its unique surface topology and more favorable charge distribution in its 20 A-long RNA binding active center cleft. In accordance with the predictions of the modeling studies, rDAP was more potent than rPAP in depurinating HIV-1 RNA. To the knowledge of the authors, this is the first structural and functional characterization of recombinant DAP.
Kurinov
Igor V
IV
Biotherapy and Drug Discovery Program, Parker Hughes Institute, St Paul, Minnesota 55113, USA.
Rajamohan
Francis
F
Uckun
Fatih M
FM
D000814:Aniline Compounds / Q000737:chemistry; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002474:Cell-Free System; D003460:Crystallization; D029749:Dianthus / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008958:Models, Molecular; D018515:Plant Leaves / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry* / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D014779:Virus Replication / Q000187:drug effects; D014961:X-Ray Diffraction
D000814:Aniline Compounds; D019380:Anti-HIV Agents; D010940:Plant Proteins; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D012313:RNA