Locations of Anti-AIDS Drug Binding Sites and Resistance Mutations in the Three-dimensional Structure of HIV-1 Reverse Transcriptase

YMDD motif in hepatitis B virus DNA polymerase influences on replication and lamivudine resistance: A study byin vitrofull-length viral DNA transfection

“…It appears that the M has close interactions with the sugar moiety of the terminal nucleotide of the template and is also potentially in a position to directly affect dNTP binding. 21 When the M is substituted, this could lead to an alteration in the positioning of the template-primer complex and dNTP binding ability. This may cause replication incompetence by changing the proper positioning of the templateprimer complex or abolishing the ability to bind dNTP.…”

“…[18][19][20][21][22][23] Amino acid substitutions in this motif were also associated with the resistance of HIV to other nucleoside analogues, such as ddC and FTC (5-fluoro-derivative of lamivudine). 21 Emergence of resistant viruses to nucleoside analogues has stimulated a heightened interest in the study of the YMDD motif, and more appropriate knowledge of HBV drugresistance patterns to lamivudine is considered imperative in improving patient management. The present study was designed to evaluate replication competence and the susceptibility to lamivudine of the YMDD motif variants of HBV in human hepatoma cells transiently transfected by full-length HBV DNA.…”

“…The YMDD motif is one of the highly conserved domains in RNAdependent DNA polymerase present in retroviruses, hepadnaviruses, retrotransposons, group II intron, bacterial retrons, and the catalytic subunit of telomerase, and is involved in nucleotide binding in the catalytic site of the polymerase. [18][19][20][21][22][23] Amino acid substitutions in this motif were also associated with the resistance of HIV to other nucleoside analogues, such as ddC and FTC (5-fluoro-derivative of lamivudine). 21 Emergence of resistant viruses to nucleoside analogues has stimulated a heightened interest in the study of the YMDD motif, and more appropriate knowledge of HBV drugresistance patterns to lamivudine is considered imperative in improving patient management.…”

Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children

“…Fax +55-21-2564.7638. E-mail: ssimonet@ioc.fiocruz.br Received 24 January 2003 accepted 25 June 2003 relative to the polymerase-binding site (Tantillo et al 1994). PIs are amprenavir (APV), indinavir (IDV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and lopinavir/ritonavir.…”

The Motif D Loop of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Is Critical for Nucleoside 5′-Triphosphate Selectivity

“…RT has a domain of two anti-parallel ␤-strands named ␤3 and ␤4 spatially equivalent to helix O of motif B. Indirect evidence suggests that this domain has the same role in nucleotide binding as motif B. Amino acid changes in this domain lead to resistance to nucleotide analogues in viral strains carrying these mutations (10), and an antibody designed to recognize an epitope located in motif B acts as a competitive inhibitor for nucleotides during polymerization (11). However, another role for the ␤3/␤4 strands was proposed in which the ␤3/␤4 strands would make contacts with the single-stranded template instead of the incoming nucleotide (12).…”