307D

Structure of a DNA analog of the primer for HIV-1 RT second strand synthesis

Summary for 307D

• Entry DOI: 10.2210/pdb307d/pdb
• Descriptor: DNA (5'-D(*CP*AP*AP*AP*GP*AP*AP*AP*AP*G)-3'), DNA (5'-D(*CP*TP*TP*TP*TP*CP*TP*TP*TP*G)-3') (3 entities in total)
• Functional Keywords: b-dna, double helix, dna
• Total number of polymer chains: 6
• Total formula weight: 18261.13

Authors

Han, G.W.,Kopka, M.L.,Cascio, D.,Grzeskowiak, K.,Dickerson, R.E. (deposition date: 1997-01-07, release date: 1997-01-27, Last modification date: 2024-04-03)

Primary citation

Han, G.W.,Kopka, M.L.,Cascio, D.,Grzeskowiak, K.,Dickerson, R.E.
Structure of a DNA analog of the primer for HIV-1 RT second strand synthesis.
J.Mol.Biol., 269:811-826, 1997

PubMed Abstract: 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.

PubMed: 9223643
DOI: 10.1006/jmbi.1997.1085

Experimental method

X-RAY DIFFRACTION (1.85 Å)