1LLN

1.6A CRYSTAL STRUCTURE OF POKEWEED ANTIVIRAL PROTEIN-III (PAP-III) WITH METHYLATED LYSINES

Summary for 1LLN

• Entry DOI: 10.2210/pdb1lln/pdb
• Related: 1QCG
• Descriptor: Antiviral Protein 3 (2 entities in total)
• Functional Keywords: pokeweed antiviral protein, ribosome inactivating protein, polynucleotide:adenosine, hydrolase
• Biological source: Phytolacca americana (American pokeweed)
• Total number of polymer chains: 1
• Total formula weight: 29683.04

Authors

Kurinov, I.V.,Uckun, F.M. (deposition date: 2002-04-29, release date: 2003-06-17, Last modification date: 2011-07-13)

Primary citation

Kurinov, I.V.,Uckun, F.M.
High resolution X-ray structure of potent anti-HIV pokeweed antiviral protein-III
Biochem.Pharm., 65:1709-1717, 2003

PubMed Abstract: Pokeweed 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.

PubMed: 12754107
DOI: 10.1016/S0006-2952(03)00144-8

Experimental method

X-RAY DIFFRACTION (1.6 Å)