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Contribution au projet de génomique structurale du virus d'Epstein-Barr : l'Uracile-ADN Glycosylase et les enzymes du métabolisme des acides nucléiques

Abstract : Epstein-Barr Virus (EBV) is a Human γ –herpesvirus. It is the causative agent of diseases such as Infectious Mononucleosis and it is associated with several immunoproliferative syndromes. Unlike other herpesviruses such as herpes-simplex, there is no treatment against EBV. EBV genome features 86 open-reading frames which are potential targets for a structural genomics approach and for the rational design of new drugs. The first round of selected targets encode for 23 proteins. The main problem we encountered was, unexpectedly, the poor expression and solubility of the majority of the selected targets. Among the 8 soluble proteins we obtained, 5 were crystallized and 4 structures were solved. The main success factor was an individual treatment of each target rather than the use of standard protocols. The Uracil-DNA Glycosylase (UNG) is a DNA repair enzyme. It was impossible to obtain crystals of the protein alone, but crystals diffracting to 2.3 Å grew upon the formation of a complex with a phage-encoded inhibitory protein. The analysis of the structure of this complex shows that the « leucin-loop », a major domain of the active site, features a 7 residue insertion which is common to all γ –herpesvirus. Despite this difference, catalytic constants are similar to other organisms UNGs, suggesting a similar interaction with DNA. Current work and problems associated with other targets is also reported (in particular on the Alkaline Exonuclease).
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https://tel.archives-ouvertes.fr/tel-00160082
Contributor : Thibault Geoui <>
Submitted on : Wednesday, July 4, 2007 - 9:20:24 PM
Last modification on : Friday, November 6, 2020 - 4:08:16 AM
Long-term archiving on: : Thursday, April 8, 2010 - 10:34:42 PM

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  • HAL Id : tel-00160082, version 1

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Thibault Geoui. Contribution au projet de génomique structurale du virus d'Epstein-Barr : l'Uracile-ADN Glycosylase et les enzymes du métabolisme des acides nucléiques. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00160082⟩

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