Sandbox Reserved 958: Difference between revisions
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In order to have a tight binding, the integrase-DNA interaction requires optimal number of contacts such as hydrogen bonds, van der Waals forces and ionic interactions between DNA elements (bases, phosphates and sugars) and amino acid chains. Among the alpha4 helix residues, <scene name='60/604477/Lys_residues_alpha4_helix/2'>Lys156 and Lys159</scene> have a main role in the specific binding of integrase to DNA by forming bidentate hydrogen bonds which are higher specific than single hydrogen bonds<ref name="Hobaika">PMID:19808934</ref>. Moreover, by being positively charged, the lysine side chain provides ionic interactions as well. In addition, Lys-rich sequence implicated in this specific interaction include these two lysines. | In order to have a tight binding, the integrase-DNA interaction requires optimal number of contacts such as hydrogen bonds, van der Waals forces and ionic interactions between DNA elements (bases, phosphates and sugars) and amino acid chains. Among the alpha4 helix residues, <scene name='60/604477/Lys_residues_alpha4_helix/2'>Lys156 and Lys159</scene> have a main role in the specific binding of integrase to DNA by forming bidentate hydrogen bonds which are higher specific than single hydrogen bonds<ref name="Hobaika">PMID:19808934</ref>. Moreover, by being positively charged, the lysine side chain provides ionic interactions as well. In addition, Lys-rich sequence implicated in this specific interaction include these two lysines. | ||
It has also be shown that <scene name='60/604477/Gln_alpha4_helix/2'>Gln148 residue</scene> contacts on adenine and cytosine of the 5' AC overhang in processed LTR<ref name="Hobaika">PMID:19808934</ref>. | It has also be shown that <scene name='60/604477/Gln_alpha4_helix/2'>Gln148 residue</scene> contacts on adenine and cytosine of the 5' AC overhang in processed LTR<ref name="Hobaika">PMID:19808934</ref>. | ||
It also seems that there is a different sensitivity to the viral DNA | It also seems that there is a different sensitivity to the viral DNA sequence (LTR) depending on the presence of Mg++ or Mn++ suggesting that specific contacts between the integrase and the viral DNA extremity are more favored in a Mg++ containing environment<ref name="Carayon">PMID:20164093</ref>. | ||
== Function == | == Function == | ||
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== Posttranslationnal Modifications == | == Posttranslationnal Modifications == | ||
Studies have prooved that 4 different kind of '''P'''ost '''T'''ranslationnal '''M'''odifications ('''PTMs''') affect the HIV-1 integrase : ubiquitination, SUMOylation, acetylation and phosphorylation. Furthermore, there are proteins that counteract or facilitate these PTMs implantation, for instance p300 and GCN5 can acetylate IN mostly on its C-ter domain on three different Lys residues (K264, K266 and K273). | Studies have prooved that 4 different kind of '''P'''ost '''T'''ranslationnal '''M'''odifications ('''PTMs''') affect the HIV-1 integrase : ubiquitination, SUMOylation, acetylation and phosphorylation. Furthermore, there are proteins that counteract or facilitate these PTMs implantation, for instance '''p300 and GCN5 can acetylate IN''' mostly on its C-ter domain on three different Lys residues (K264, K266 and K273). | ||
[[Image:1742-4690-7-18-7.jpg]] | [[Image:1742-4690-7-18-7.jpg]] | ||