Exploring HIV Integrase 3’-processing Using Designed DNA Substrates and Structural Study of HIV DNA Hairpins

In the HIV viral integration procedure, 3’-processing of the viral DNA by the integrase enzyme is an essential first step which is followed by the integration of viral DNA into the host genome. In 3’-processing, the integrase cleaves the backbone of the DNA substrate on the 3’ end of a conserved CA...

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Bibliographic Details
Main Author: Li, Qiushi
Format: Others
Published: ScholarWorks @ Georgia State University 2016
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Online Access:http://scholarworks.gsu.edu/chemistry_theses/96
http://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1097&context=chemistry_theses
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Summary:In the HIV viral integration procedure, 3’-processing of the viral DNA by the integrase enzyme is an essential first step which is followed by the integration of viral DNA into the host genome. In 3’-processing, the integrase cleaves the backbone of the DNA substrate on the 3’ end of a conserved CA dinucleotide motif and inserts a helix between the two DNA strands, forcing them apart (Hare, S., 2012). Our study confirms that the presence of a G-amino group is crucial for 3’-processing. Substituting inosine for G in the CA step removes this amino group and results in loss of enzyme activity. Further work showed that the presence of a terminal duplex segment is not required for 3’-processing. Additional substrate modifications are studied in order to evaluate the actual importance of the CA step.