307d

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.