Sunday, December 16, 2007

Reverse Transcriptase, Integrase and More

A helpful tutorial about HIV-1 reverse transcriptase can be accessed here. While the focus of the link is the reverse transcriptase of a particular retrovirus there is information applicable to reverse transcriptases a whole. Reverse transcriptases are viral enzymes that enable retroviruses to transform their RNA genomes into DNA within the host organism. Here is another informative link.

Another important enzyme for retroviruses is integrase.Integrase mediates integration of a DNA copy of the viral genome into the host chromosome. Integrase is composed of three domains. The amino-terminal domain is a zinc binding domain. The central domain is the catalytic domain Pfam:PF00665. This domain is the carboxyl terminal domain that is a non-specific DNA binding domain.1 HIV specific integrase is discussed at this link.

Irreversible Inhibition of Human Immunodeficiency Virus Type 1 Integrase by Dicaffeoylquinic Acids is a paper suggesting that the function of integrase makes it an attractive target for antiretroviral agents.

One of the chief characteristics of the retroviral life cycle is integration of viral genetic information into the genome of the host cell, forming the provirus. The provirus embodies a permanent association between cell and retrovirus. Integration into a chromosome of a germ cell provides the means for retroviruses to colonize the germ line of their hosts, where they can persist as stable integrated proviruses for multiple generations. Such elements are known as endogenous retroviruses. Analysis of genomic DNA reveals the presence of many thousands of retroviruses or retroviral-like elements, indicating that the products of reverse transcription have played a major part in shaping the eukaryotic genome.2


References:

1. Sanger Institute; Pfam; Family: Integrase (PF00552); http://pfam.sanger.ac.uk/family?id=Integrase; PubMed; An Integrase DNA binding domain summary lists the following as the source:

Lodi PJ, Ernst JA, Kuszewski J, Hickman AB, Engelman A, Craigie R, Clore GM, Gronenborn AM; , Biochemistry 1995;34:9826-9833.: Solution structure of the DNA binding domain of HIV-1 integrase.

2. Retroviruses at the National Center for Biotechnology Information; John M. Coffin, Stephen H. Hughes and Harold E. Varmus; Cold Spring Harbor Laboratory Press; http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=rv.section.3432

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