From Wikipedia, the free encyclopedia

Integrase is an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell.

It is a key component in the pre-integration complex (PIC).

Contents 1 Structure 2 Function 3 HIV integrase 4 Reference 5 External links

The integrase protein contains three domains:

• an N-terminal HH-CC zinc finger domain believed to be partially responsible for multimerization,
• a central catalytic domain
• an C-terminal DNA binding domain.

Biochemical data and structural data suggest that integrase functions as a dimer or a tetramer.

Additionally, several host cellular proteins have been shown to interact with integrase and may facilitate the integration process.

Integration occurs following production of the double-stranded viral DNA by the viral DNA polymerase, reverse transcriptase.

Integrase acts to insert the proviral DNA into the host chromosomal DNA, a step which is essential for HIV replication.

Integrase catalyzes two reactions;

• 3'-end processing, in which two deoxynucleotides are removed from the 3' ends of the viral DNA.
• the strand transfer reaction, in which the processed 3' ends of the viral DNA are covalently ligated to the host chromosomal DNA.

Integration of the proviral DNA is essential for the subsequent transcription of the viral genome which leads to production of new viral genomic RNA and viral proteins needed for the production of the next round of infectious virus.

Essentially, integrase is a key step in allowing viral DNA to become a permanent member of the host genome. This integrated proviral DNA is then translated using host cell machinery (see translation) into viral proteins.

HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product. Integrase, therefore, is an attractive potential target for new anti-HIV therapeutics.

In November 2005, data from a phase 2 study of an investigational HIV integrase inhibitor, MK-0518, demonstrated that the compound had potent antiviral activity, and the manufacturer, Merck, is undertaking further clinical studies. ^[1][2]

It is important to note that there still are currently no FDA approved drugs available to the public.

1. ^ Morales-Ramirez JO, Teppler H, Kovacs C, et al. Antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, in ART-naïve HIV-1 infected patients. Program and abstracts of the 10th European AIDS Conference; November 17-20, 2005; Dublin, Ireland. Abstract LBPS1/6. Online summary: http://clinicaloptions.com/HIV/Conference%20Coverage/Dublin%202005/Capsules/LBPS1-6.aspx
2. ^ Savarino A. A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin Investig Drugs. 2006 Dec;15(12):1507-22.

• MeSH Integrases