STRUCTURE-FUNCTION RELATION IN HIV REVERSE TRANSCRIPTION

Project Details

Description

Reverse transcriptase is an integral part of many oncogenic
viruses, including those from human leukemia and AIDS virus, which
is essential for viral replication. Long range goals of this
proposal are to understand and define the biochemical,
enzymological and structural properties of reverse transcriptase
so that molecular mechanisms underlying reverse transcription could
be clarified. The major objective, therefore, of this research is
to identify and define structural domains of reverse transcriptase
which are involved in the binding of substrate dNTPs and template-
primer as well as those responsible for the expression of reverse-
transcriptase associated Ribonuclease H. The results are expected
to clarify the basic mechanisms of enzymatic synthesis of DNA
catalyzed by reverse transcriptase and may provide an insight into
unique properties/structures which may help in designing the
potential therapeutic agents. We have analyzed mechanism of anti-reverse transcriptase activity
of a number of inhibitors and have identified some reagents which
appear to react with reverse transcriptase in a site-specific
manner. In addition, we have standardized protocols for covalently
linking substrates, template-primers and specific reagents to the
enzyme protein. These reagents are quite useful in establishment
of site-specific covalent modification of RT which in turn will
permit labeling, identification and isolation of peptides carrying
these sites. In this manner, we hope to identify domains
responsible for the polymerase and RNAse H activity of MuLV and HIV
reverse transcriptase. This knowledge will be very useful in
understanding of precise mechanisms of many anti-viral (including
anti-AIDS) drugs with presumptive anti-RT activity.
StatusFinished
Effective start/end date6/1/895/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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