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PDBsum entry 4b3p
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Hydrolase/RNA/DNA
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PDB id
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4b3p
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References listed in PDB file
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Key reference
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Title
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Complexes of HIV-1 rt, Nnrti and RNA/DNA hybrid reveal a structure compatible with RNA degradation.
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Authors
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M.Lapkouski,
L.Tian,
J.T.Miller,
S.F.Le grice,
W.Yang.
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Ref.
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Nat Struct Biol, 2013,
20,
230-236.
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PubMed id
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Abstract
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Hundreds of structures of type 1 human immunodeficiency virus (HIV-1) reverse
transcriptase (RT) have been determined, but only one contains an RNA/DNA
hybrid. Here we report three structures of HIV-1 RT complexed with a
non-nucleotide RT inhibitor (NNRTI) and an RNA/DNA hybrid. In the presence of an
NNRTI, the RNA/DNA structure differs from all prior nucleic acid-RT structures
including the RNA/DNA hybrid. The enzyme structure also differs from all
previous RT-DNA complexes. Thus, the hybrid has ready access to the RNase-H
active site. These observations indicate that an RT-nucleic acid complex may
adopt two structural states, one competent for DNA polymerization and the other
for RNA degradation. RT mutations that confer drug resistance but are distant
from the inhibitor-binding sites often map to the unique RT-hybrid interface
that undergoes conformational changes between two catalytic states.
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