1lln
1.6A CRYSTAL STRUCTURE OF POKEWEED ANTIVIRAL PROTEIN-III (PAP-III) WITH METHYLATED LYSINES
Structural highlights
FunctionRIP2_PHYAM Inhibits viral infection of plants. Inhibits protein synthesis in both prokaryotes and eukaryotes. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPokeweed antiviral protein III (PAP-III), a naturally occurring protein isolated from late summer leaves of the pokeweed plant (Phytolacca americana), has potent anti-HIV activity by an as yet undetermined molecular mechanism. PAP-III belongs to a family of ribosome-inactivating proteins that catalytically deadenylate ribosomal and viral RNA. The chemical modification of PAP-III by reductive methylation of its lysine residues significantly improved the crystal quality for X-ray diffraction studies. Trigonal crystals of the modified PAP-III, with unit cell parameters a=b=80.47A, c=76.21A, were obtained using 30% PEG400 as the precipitant. These crystals contained one enzyme molecule per asymmetric unit and diffracted up to 1.5A, when exposed to a synchrotron source. Here we report the X-ray crystal structure of PAP-III at 1.6A resolution, which was solved by molecular replacement using the homology model of PAP-III as a search model. The fold typical of other ribosome-inactivating proteins is conserved, despite several differences on the surface and in the loop regions. Residues Tyr(69), Tyr(117), Glu(172), and Arg(175) are expected to define the active site of PAP-III. Molecular modeling studies of the interactions of PAP-III and PAP-I with a single-stranded RNA heptamer predicted a more potent anti-HIV activity for PAP-III due to its unique surface topology and more favorable charge distribution in its 20A-long RNA binding active center cleft. In accordance with the predictions of the modeling studies, PAP-III was more potent than PAP-I in depurinating HIV-1 RNA. High resolution X-ray structure of potent anti-HIV pokeweed antiviral protein-III.,Kurinov IV, Uckun FM Biochem Pharmacol. 2003 May 15;65(10):1709-17. PMID:12754107[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||
