1lln: Difference between revisions

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

OverviewOverview

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.

About this StructureAbout this Structure

1LLN is a Single protein structure of sequence from Phytolacca americana. Active as rRNA N-glycosylase, with EC number 3.2.2.22 Full crystallographic information is available from OCA.

ReferenceReference

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

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 '''1.6A CRYSTAL STRUCTURE OF POKEWEED ANTIVIRAL PROTEIN-III (PAP-III) WITH METHYLATED LYSINES'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-LLN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Phytolacca_americana Phytolacca americana]. Active as [http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LLN OCA].
+LLN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Phytolacca_americana Phytolacca americana]. Active as [http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LLN OCA].
 ==Reference==
@@ Line 15: / Line 14: @@
 [[Category: Single protein]]
 [[Category: rRNA N-glycosylase]]
-[[Category: Kurinov, I.V.]]
+[[Category: Kurinov, I V.]]
-[[Category: Uckun, F.M.]]
+[[Category: Uckun, F M.]]
 [[Category: pokeweed antiviral protein]]
 [[Category: polynucleotide:adenosine]]
 [[Category: ribosome inactivating protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:17:19 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:46:05 2008''