Sandbox Reserved 958: Difference between revisions
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- ''in vivo'' it catalyzes the '''transport the viral DNA into the nucleus''', it interacts with many proteins ('''VPR, VBP1, HIV-matrix,...''') and DNA to form the '''Pre-Integration Complex''' ('''PIC''') and allow the integration of the viral DNA into host genome and this mechanism can be divided in two reactions, the '''3'-Processing''' and the '''Strand Transfer'''<ref name="Dells">PMID: 19091057</ref> | - ''in vivo'' it catalyzes the '''transport the viral DNA into the nucleus''', it interacts with many proteins ('''VPR, VBP1, HIV-matrix,...''') and DNA to form the '''Pre-Integration Complex''' ('''PIC''') and allow the integration of the viral DNA into host genome and this mechanism can be divided in two reactions, the '''3'-Processing''' and the '''Strand Transfer'''<ref name="Dells">PMID: 19091057</ref> | ||
[[Image:3108751 idr-4-065f1.png]] | [[Image:3108751 idr-4-065f1.png | thumb | upright=3]] | ||
- ''in vitro'' researchers proved that two more reactions can be catalyzed by the integrase, the '''disintegration''' of the viral DNA and also a possible '''DNA polymerase activity'''<ref name="Liao">PMID:21426159</ref> to repair mismatches during integration. | - ''in vitro'' researchers proved that two more reactions can be catalyzed by the integrase, the '''disintegration''' of the viral DNA and also a possible '''DNA polymerase activity'''<ref name="Liao">PMID:21426159</ref> to repair mismatches during integration. | ||
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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 | thumb | upright=3]] | ||
In contrary Ku70 reduces the ubiquitination level of the N-ter domain (K6, K11, K27, K29, K33, K48 and K63). Another study also found that IN contains three ψ-K-x-D/E motifs, which can be SUMOylated at three Lys residues, K46,<scene name='60/604477/Sumoylation/1'>K136</scene> and K244 <ref name="Terreni">PMID:20226045</ref>. | In contrary '''Ku70 reduces the ubiquitination level''' of the N-ter domain (K6, K11, K27, K29, K33, K48 and K63). Another study also found that IN contains '''three ψ-K-x-D/E motifs''', which can be SUMOylated at three Lys residues, K46,<scene name='60/604477/Sumoylation/1'>K136</scene> and K244 <ref name="Terreni">PMID:20226045</ref>. | ||
==Inhibitors== | ==Inhibitors== | ||
Since few years, HIV-1 is an important therapeutic target. Actually there are two kind of inhibitors: the '''I'''ntegrase '''S'''trand '''T'''ransfer '''I'''nhibitors ('''INSTIs''' ) and the '''IN'''tegrase DNA-'''B'''inding '''I'''nhibitors '''(INBIs)'''. Over the past 5 years, INSTIs have been shown significant results as antiviral compounds with in 2007, the licensing of the first integrase inhibitor called '''raltegravir''', which target the integrase active site and thus, inhibit DNA strand transfer. However, resistance to this compound emerges which in turn confers the same effect to the second licensed INSTI, '''elvitegravir'''<ref name="Engelman">PMID: 23647983</ref>. | Since few years, HIV-1 is an important therapeutic target. Actually there are two kind of inhibitors: the '''I'''ntegrase '''S'''trand '''T'''ransfer '''I'''nhibitors ('''INSTIs''' ) and the '''IN'''tegrase DNA-'''B'''inding '''I'''nhibitors '''(INBIs)'''. Over the past 5 years, INSTIs have been shown significant results as antiviral compounds with in 2007, the licensing of the first integrase inhibitor called '''raltegravir''', which target the integrase active site and thus, inhibit DNA strand transfer. However, resistance to this compound emerges which in turn confers the same effect to the second licensed INSTI, '''elvitegravir'''<ref name="Engelman">PMID: 23647983</ref>. | ||