1ra7
From Proteopedia
(New page: 200px<br /><applet load="1ra7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ra7, resolution 2.35Å" /> '''Poliovirus Polymeras...) |
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| - | [[Image:1ra7.jpg|left|200px]]<br /><applet load="1ra7" size=" | + | [[Image:1ra7.jpg|left|200px]]<br /><applet load="1ra7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ra7, resolution 2.35Å" /> | caption="1ra7, resolution 2.35Å" /> | ||
'''Poliovirus Polymerase with GTP'''<br /> | '''Poliovirus Polymerase with GTP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The active RNA-dependent RNA polymerase of poliovirus, 3Dpol, is generated | + | The active RNA-dependent RNA polymerase of poliovirus, 3Dpol, is generated by cleavage of the 3CDpro precursor protein, a protease that has no polymerase activity despite containing the entire polymerase domain. By intentionally disrupting a known and persistent crystal packing interaction, we have crystallized the poliovirus polymerase in a new space group and solved the complete structure of the protein at 2.0 A resolution. It shows that the N-terminus of fully processed 3Dpol is buried in a surface pocket where it makes hydrogen bonds that act to position Asp238 in the active site. Asp238 is an essential residue that selects for the 2' OH group of substrate rNTPs, as shown by a 2.35 A structure of a 3Dpol-GTP complex. Mutational, biochemical, and structural data further demonstrate that 3Dpol activity is exquisitely sensitive to mutations at the N-terminus. This sensitivity is the result of allosteric effects where the structure around the buried N-terminus directly affects the positioning of Asp238 in the active site. |
==About this Structure== | ==About this Structure== | ||
| - | 1RA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_poliovirus_1 Human poliovirus 1] with GTP and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] Full crystallographic information is available from [http:// | + | 1RA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_poliovirus_1 Human poliovirus 1] with <scene name='pdbligand=GTP:'>GTP</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RA7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Peersen, O | + | [[Category: Peersen, O B.]] |
| - | [[Category: Thompson, A | + | [[Category: Thompson, A A.]] |
[[Category: ACY]] | [[Category: ACY]] | ||
[[Category: GTP]] | [[Category: GTP]] | ||
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[[Category: rna-dependent]] | [[Category: rna-dependent]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:48:41 2008'' |
Revision as of 12:48, 21 February 2008
|
Poliovirus Polymerase with GTP
Overview
The active RNA-dependent RNA polymerase of poliovirus, 3Dpol, is generated by cleavage of the 3CDpro precursor protein, a protease that has no polymerase activity despite containing the entire polymerase domain. By intentionally disrupting a known and persistent crystal packing interaction, we have crystallized the poliovirus polymerase in a new space group and solved the complete structure of the protein at 2.0 A resolution. It shows that the N-terminus of fully processed 3Dpol is buried in a surface pocket where it makes hydrogen bonds that act to position Asp238 in the active site. Asp238 is an essential residue that selects for the 2' OH group of substrate rNTPs, as shown by a 2.35 A structure of a 3Dpol-GTP complex. Mutational, biochemical, and structural data further demonstrate that 3Dpol activity is exquisitely sensitive to mutations at the N-terminus. This sensitivity is the result of allosteric effects where the structure around the buried N-terminus directly affects the positioning of Asp238 in the active site.
About this Structure
1RA7 is a Single protein structure of sequence from Human poliovirus 1 with and as ligands. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.
Reference
Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase., Thompson AA, Peersen OB, EMBO J. 2004 Sep 1;23(17):3462-71. Epub 2004 Aug 12. PMID:15306852
Page seeded by OCA on Thu Feb 21 14:48:41 2008
