1sj4
From Proteopedia
(New page: 200px<br /> <applet load="1sj4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sj4, resolution 2.70Å" /> '''Crystal structure o...) |
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| - | [[Image:1sj4.gif|left|200px]]<br /> | + | [[Image:1sj4.gif|left|200px]]<br /><applet load="1sj4" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1sj4, resolution 2.70Å" /> | caption="1sj4, resolution 2.70Å" /> | ||
'''Crystal structure of a C75U mutant Hepatitis Delta Virus ribozyme precursor, in Cu2+ solution'''<br /> | '''Crystal structure of a C75U mutant Hepatitis Delta Virus ribozyme precursor, in Cu2+ solution'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ribozymes enhance chemical reaction rates using many of the same catalytic | + | Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes. |
==About this Structure== | ==About this Structure== | ||
| - | 1SJ4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_delta_virus Hepatitis delta virus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1SJ4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_delta_virus Hepatitis delta virus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SJ4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cate, J | + | [[Category: Cate, J H.]] |
[[Category: Ding, F.]] | [[Category: Ding, F.]] | ||
| - | [[Category: Doudna, J | + | [[Category: Doudna, J A.]] |
[[Category: Ke, A.]] | [[Category: Ke, A.]] | ||
[[Category: Zhou, K.]] | [[Category: Zhou, K.]] | ||
[[Category: hdv; ribozyme; rna; u1a; precurosr]] | [[Category: hdv; ribozyme; rna; u1a; precurosr]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:07 2008'' |
Revision as of 13:02, 21 February 2008
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Crystal structure of a C75U mutant Hepatitis Delta Virus ribozyme precursor, in Cu2+ solution
Overview
Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.
About this Structure
1SJ4 is a Single protein structure of sequence from Hepatitis delta virus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
A conformational switch controls hepatitis delta virus ribozyme catalysis., Ke A, Zhou K, Ding F, Cate JH, Doudna JA, Nature. 2004 May 13;429(6988):201-5. PMID:15141216
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