Sandbox Reserved 958: Difference between revisions
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[[Image:3108751 idr-4-065f1.png]] | [[Image:3108751 idr-4-065f1.png]] | ||
== Posttranslationnal Modifications == | == Posttranslationnal Modifications == | ||
Studies have prooved that 4 different kind of Post Translationnal Modifications (PTMs) affect the HIV-1 integrase : ubiquitination, SUMOylation, acetylation and phosphorylation. Furthermore there are proteins that counteract or facilitate these PTMs implantation. On one hand p300 and GCN5 can acetylate IN mostly on its C-ter domain while in the other hand 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. | Studies have prooved that 4 different kind of Post Translationnal Modifications (PTMs) affect the HIV-1 integrase : ubiquitination, SUMOylation, acetylation and phosphorylation. Furthermore there are proteins that counteract or facilitate these PTMs implantation. On one hand p300 and GCN5 can acetylate IN mostly on its C-ter domain while in the other hand 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="Mbisa">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>. | ||