The reverse transcriptase is an obligatory enzyme in the life cycle of retroviruses. The HIV reverse transcriptase is a logical target for specific and potent chemical inhibitors which may be useful in the treatment of Acquired Immune Deficiency Syndrome (AIDS). We have initiated biophysical analysis of the avian retrovirus reverse transcriptase. The avian alpha beta DNA polymerase is a two subunit enzyme requiring Mg2+, properties closely aligned with the HIV reverse transcriptase. In collaboration with Dr. Steve Harrison, we propose to crystallize the alpha beta DNA polymerase which can be readily purified in 10-12 mg lots. The detailed evaluation of the tertiary structure of the crystallized alpha beta enzyme at various stages of resolution along with our other proposed biochemical and genetic analyses of the alpha subunit associated DNA polymerase and RNase H active sites should permit the development of an accurate protein model. Understanding the protein conformation of reverse transcriptase should be very helpful in improving and developing chemical inhibitors of this obligatory enzyme of retroviruses.
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