Chimeric human immunodeficiency virus type 1/type 2 reverse transcriptases display reversed sensitivity to nonnucleoside analog inhibitors.

作者: C. K. Shih , J. M. Rose , G. L. Hansen , J. C. Wu , A. Bacolla

DOI: 10.1073/PNAS.88.21.9878

关键词: Enzyme inhibitorVirusVirologyBiologyEnzymeAmino acidBinding siteTyrosineReverse transcriptaseAffinity label

摘要: Abstract Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), an important therapeutic target in the treatment of AIDS, is effectively inhibited by a class nonnucleoside analog compounds that includes nevirapine (BI-RG-587) and tetrahydroimidazo[4,5,1-jk]-[1,4]benzodiazepin-2(1H)-one -thione. We show both tyrosine residues at positions 181 188 flanking putative catalytic site HIV-1 RT are required for sensitivity enzyme to these compounds. HIV-2 RT, which does not have tyrosines positions, resistant inhibitors. Substitution amino acid position or into results while retaining 3'-azido-2',3'-dideoxythymidine triphosphate. substituted with acids 176-190 from acquires

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