307d
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STRUCTURE OF A DNA ANALOG OF THE PRIMER FOR HIV-1 RT SECOND STRAND SYNTHESIS
OverviewOverview
The non-self-complementary DNA decamer, C-A-A-A-G-A-A-A-A-G/C-T-T-T-T-C-T-T-T-G is a DNA/DNA analogue of a portion, of the polypurine tract or PPT, which is a RNA/DNA hybrid that serves as a, primer for synthesis of the (+) DNA strand by HIV reverse transcriptase, (RT), and which is not digested by the RNase H domain of reverse, transcriptase following (-) strand synthesis. The same unusual, conformation that eludes RNase H, thought to be a change in width of minor, groove, may also be responsible for the inhibition of HIV RT by minor, groove binding drugs such as distamycin and their bis-linked derivatives., The present X-ray crystal structure of this DNA decamer exhibits the usual, properties of A-tract B-DNA under biologically relevant conditions: large, propeller twist of base-pairs, narrowed minor groove, and a straight helix, axis. Groove narrowing is fully developed in the A-A-A-A region, but not, in the A-A-A region, which previous investigators have proposed as being, too short to exhibit typical A-tract properties. The RNA/DNA hybrid, produced by HIV reverse transcriptase during (-) strand synthesis, presumably forms a "heteromerous" or H-helix with narrower minor groove, than an A-helical RNA/RNA duplex. If the narrowing of minor groove in, A-tract H-helices is comparable to that seen in A-tract B-helices, then, the narrowed minor groove of the polypurine tract could make the second, primer site both (1) impervious to RNase H digestion, and (2) susceptible, to inhibition by minor groove binding drugs.
About this StructureAbout this Structure
307D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Structure of a DNA analog of the primer for HIV-1 RT second strand synthesis., Han GW, Kopka ML, Cascio D, Grzeskowiak K, Dickerson RE, J Mol Biol. 1997 Jun 27;269(5):811-26. PMID:9223643
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