Crystal structures of Zidovudine- or Lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215.

Chamberlain PP, Ren J, Nichols CE, Douglas L, Lennerstrand J, Larder BA, Stuart DI, Stammers DK
J Virol (2002), Volume 76, Page 10015
PubMed entry Full article text

Abstract:

Six structures of human immunodeficiency virus type 1 (HIV-1) reverse ...
Six structures of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing combinations of resistance mutations for zidovudine (AZT) (M41L and T215Y) or lamivudine (M184V) have been determined as inhibitor complexes. Minimal conformational changes in the polymerase or nonnucleoside RT inhibitor sites compared to the mutant RTMC (D67N, K70R, T215F, and K219N) are observed, indicating that such changes may occur only with certain combinations of mutations. Model building M41L and T215Y into HIV-1 RT-DNA and docking in ATP that is utilized in the pyrophosphorolysis reaction for AZT resistance indicates that some conformational rearrangement appears necessary in RT for ATP to interact simultaneously with the M41L and T215Y mutations.

Polymerases:

HIV RT,HIV RT M41LD67N/K70R/M184V/T215Y,HIV RT M41LT215Y,HIV RT M184V,HIV RT T215Y

Topics:

Structure and Structure/Function

Status:

new topics/pols set partial results complete validated

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Structures:

1LWF 1LWE 1LWC 1LW2 1LW0

Version:20241218

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