Retrovirus Reverse Transcriptases Containing a Modified YXDD Motif

Abstract

The YXDD motif, where X is a variable amino acid, is highly conserved among various viral RNA-dependent DNA polymerases. Mutations in the YXDD motif can abolish enzymatic activity, alter the processivity and fidelity of enzymes and decrease virus infectivity. This review provides a summary of the significant documented studies on the YXDD motif of HIV-1, simian immunodeficiency virus, feline immunodeficiency virus and murine leukaemia virus and the impact of mutation that this motif has had on viral pathogenesis and drug treatment.

Genomically encoded analog memory with precise in vivo DNA writing in living cell populations

“…S1). To verify that ssDNA expression depended on RT activity, point mutations [Asp 197 →Ala 197 (D197A) and D198A] were introduced to the active site of the RT to make a catalytically dead RT (dRT) (23). This modification completely abolished ssDNA production (Fig.…”

Phage-assisted evolution and protein engineering yield compact, efficient prime editors

“…Additionally, we previously installed D200N to create PE2 from the wild-type M-MLV RT, 1 and V223 is part of the core YXDD motif that has been implicated in the activities of various RTs. 37 We tested evolved and engineered mutations at these residues, then combined the most promising candidates to generate an RNaseH-truncated evolved and engineered M-MLV variant that we designated PE6d ( Figure S4 A).

Figure S4 Development and characterization of highly processive, dual AAV-compatible RTs, related to Figure 4 (A) Editing efficiencies of prime editors containing single M-MLV mutants in HEK293T cells.

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Construction of A Preliminary Three-Dimensional Structure Simian betaretrovirus Serotype-2 (SRV-2) Reverse Transcriptase Isolated from Indonesian Cynomolgus Monkey

“…The polymerase active site that is located in the finger/palm subdomain is characterised by three conserved catalytic aspartates at the position of Asp90, Asp165, Asp166 for SRV-2 RT Mf ET1006, and Asp110, Asp185, Asp186 for HIV-1 RT ( Table 2 ). This triad aspartates (the last two residues are part of Y X DD motif), play a significant role in the HIV-1 RT enzymatic catalytic through the binding to the divalent cation Mg 2+ ( Sharma et al . 2005 ).…”

“…The conserved motif of SRV-2 RT Mf ET1006 and HIV-1 RT consists of four amino acids, YMDD for Tyr, Met, Asp, Asp at the position 163–166 for SRV-2 RT Mf ET1006 and 183–186 for HIV-1 RT. SRV-2 RT Mf ET1006 has a YMDD amino acid motif similar with HIV-1, SIV and FIV, however, it was different from YVDD motif that MMLV and FeLV have ( Sharma et al . 2005 ).…”

“…2005 ). Recently, many studies focused on this Y X DD motif due to its significance in NRTI resistance, RT fidelity, polymerase process, and viral replication ( Sharma et al . 2005 ).…”