1t05
From Proteopedia
(New page: 200px<br /> <applet load="1t05" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t05, resolution 3.0Å" /> '''HIV-1 reverse transc...) |
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| - | [[Image:1t05.gif|left|200px]]<br /> | + | [[Image:1t05.gif|left|200px]]<br /><applet load="1t05" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t05" size=" | + | |
caption="1t05, resolution 3.0Å" /> | caption="1t05, resolution 3.0Å" /> | ||
'''HIV-1 reverse transcriptase crosslinked to template-primer with tenofovir-diphosphate bound as the incoming nucleotide substrate'''<br /> | '''HIV-1 reverse transcriptase crosslinked to template-primer with tenofovir-diphosphate bound as the incoming nucleotide substrate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Tenofovir, also known as PMPA, R-9-(2-(phosphonomethoxypropyl)adenine, is | + | Tenofovir, also known as PMPA, R-9-(2-(phosphonomethoxypropyl)adenine, is a nucleotide reverse transcriptase (RT) inhibitor. We have determined the crystal structures of two related complexes of HIV-1 RT with template primer and tenofovir: (i) a ternary complex at a resolution of 3.0 A of RT crosslinked to a dideoxy-terminated DNA with tenofovir-diphosphate bound as the incoming substrate; and (ii) a RT-DNA complex at a resolution of 3.1 A with tenofovir at the 3' primer terminus. The tenofovir nucleotide in the tenofovir-terminated structure seems to adopt multiple conformations. Some nucleoside reverse transcriptase inhibitors, including 3TC and AZT, have elements ('handles') that project beyond the corresponding elements on normal dNTPs (the 'substrate envelope'). HIV-1 RT resistance mechanisms to AZT and 3TC take advantage of these handles; tenofovir's structure lacks handles that could protrude through the substrate envelope to cause resistance. |
==About this Structure== | ==About this Structure== | ||
| - | 1T05 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with MG, TNV and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http:// | + | 1T05 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=TNV:'>TNV</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T05 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Arnold, E.]] | [[Category: Arnold, E.]] | ||
[[Category: Ding, J.]] | [[Category: Ding, J.]] | ||
| - | [[Category: Sarafianos, S | + | [[Category: Sarafianos, S G.]] |
[[Category: Tuske, S.]] | [[Category: Tuske, S.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: tenofovir]] | [[Category: tenofovir]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:08:16 2008'' |
Revision as of 13:08, 21 February 2008
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HIV-1 reverse transcriptase crosslinked to template-primer with tenofovir-diphosphate bound as the incoming nucleotide substrate
Overview
Tenofovir, also known as PMPA, R-9-(2-(phosphonomethoxypropyl)adenine, is a nucleotide reverse transcriptase (RT) inhibitor. We have determined the crystal structures of two related complexes of HIV-1 RT with template primer and tenofovir: (i) a ternary complex at a resolution of 3.0 A of RT crosslinked to a dideoxy-terminated DNA with tenofovir-diphosphate bound as the incoming substrate; and (ii) a RT-DNA complex at a resolution of 3.1 A with tenofovir at the 3' primer terminus. The tenofovir nucleotide in the tenofovir-terminated structure seems to adopt multiple conformations. Some nucleoside reverse transcriptase inhibitors, including 3TC and AZT, have elements ('handles') that project beyond the corresponding elements on normal dNTPs (the 'substrate envelope'). HIV-1 RT resistance mechanisms to AZT and 3TC take advantage of these handles; tenofovir's structure lacks handles that could protrude through the substrate envelope to cause resistance.
About this Structure
1T05 is a Protein complex structure of sequences from Human immunodeficiency virus 1 with , and as ligands. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
Reference
Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir., Tuske S, Sarafianos SG, Clark AD Jr, Ding J, Naeger LK, White KL, Miller MD, Gibbs CS, Boyer PL, Clark P, Wang G, Gaffney BL, Jones RA, Jerina DM, Hughes SH, Arnold E, Nat Struct Mol Biol. 2004 May;11(5):469-74. Epub 2004 Apr 25. PMID:15107837
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