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Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors.

Abstract:

Trp-229 is part of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-binding pocket of HIV type 1 (HIV-1) reverse transcriptase (RT), and is also part of the "primer grip" of HIV-1 RT. Using site-directed mutagenesis, seven RT mutants were constructed bearing the mutations 229Phe, 229Tyr, 229Ile, 229His, 229Lys, 229Cys, and 229Gln. We found that all of the mutants showed severely compromised RNA- and DNA-dependent DNA polymerase activities (<2% of wild-type activity). The recombin...

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Publication status:
Published

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Authors


Pelemans, H More by this author
De Clercq, E More by this author
Balzarini, J More by this author
Journal:
Molecular pharmacology
Volume:
57
Issue:
5
Pages:
954-960
Publication date:
2000-05-05
EISSN:
1521-0111
ISSN:
0026-895X
URN:
uuid:828d599c-e9bc-4431-8f42-746c4ca2efc2
Source identifiers:
24212
Local pid:
pubs:24212

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