307d
From Proteopedia
(New page: 200px<br /> <applet load="307d" size="450" color="white" frame="true" align="right" spinBox="true" caption="307d, resolution 1.850Å" /> '''STRUCTURE OF A DNA...) |
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| - | [[Image:307d.gif|left|200px]]<br /> | + | [[Image:307d.gif|left|200px]]<br /><applet load="307d" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="307d" size=" | + | |
caption="307d, resolution 1.850Å" /> | caption="307d, resolution 1.850Å" /> | ||
'''STRUCTURE OF A DNA ANALOG OF THE PRIMER FOR HIV-1 RT SECOND STRAND SYNTHESIS'''<br /> | '''STRUCTURE OF A DNA ANALOG OF THE PRIMER FOR HIV-1 RT SECOND STRAND SYNTHESIS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The non-self-complementary DNA decamer | + | 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 Structure== | ==About this Structure== | ||
| - | 307D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 307D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=307D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Cascio, D.]] | [[Category: Cascio, D.]] | ||
| - | [[Category: Dickerson, R | + | [[Category: Dickerson, R E.]] |
[[Category: Grzeskowiak, K.]] | [[Category: Grzeskowiak, K.]] | ||
| - | [[Category: Han, G | + | [[Category: Han, G W.]] |
| - | [[Category: Kopka, M | + | [[Category: Kopka, M L.]] |
[[Category: b-dna]] | [[Category: b-dna]] | ||
[[Category: double helix]] | [[Category: double helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:01:52 2008'' |
Revision as of 17:01, 21 February 2008
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STRUCTURE OF A DNA ANALOG OF THE PRIMER FOR HIV-1 RT SECOND STRAND SYNTHESIS
Overview
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 Structure
307D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
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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