2i5j
From Proteopedia
(New page: 200px<br /> <applet load="2i5j" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i5j, resolution 3.150Å" /> '''Crystal structure ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2i5j.gif|left|200px]]<br /> | + | [[Image:2i5j.gif|left|200px]]<br /><applet load="2i5j" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2i5j" size=" | + | |
caption="2i5j, resolution 3.150Å" /> | caption="2i5j, resolution 3.150Å" /> | ||
'''Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor'''<br /> | '''Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2I5J 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 GLC, SUC, MG and K05 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:// | + | 2I5J 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=GLC:'>GLC</scene>, <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=K05:'>K05</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=2I5J OCA]. |
==Reference== | ==Reference== | ||
| Line 35: | Line 34: | ||
[[Category: structure-based drug design]] | [[Category: structure-based drug design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:30:46 2008'' |
Revision as of 13:30, 23 January 2008
|
Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor
Overview
The rapid emergence of drug-resistant variants of human immunodeficiency, virus, type 1 (HIV-1), has limited the efficacy of anti-acquired immune, deficiency syndrome (AIDS) treatments, and new lead compounds that target, novel binding sites are needed. We have determined the 3.15 A resolution, crystal structure of HIV-1 reverse transcriptase (RT) complexed with, dihydroxy benzoyl naphthyl hydrazone (DHBNH), an HIV-1 RT RNase H (RNH), inhibitor (RNHI). DHBNH is effective against a variety of drug-resistant, HIV-1 RT mutants. While DHBNH has little effect on most aspects of, RT-catalyzed DNA synthesis, at relatively high concentrations it does, inhibit the initiation of RNA-primed DNA synthesis. Although primarily an, RNHI, DHBNH binds >50 A away from the RNH active site, at a novel site, near both the polymerase active site and the non-nucleoside RT inhibitor, (NNRTI) binding pocket. When DHBNH binds, both Tyr181 and Tyr188 remain in, the conformations seen in unliganded HIV-1 RT. DHBNH interacts with, conserved residues (Asp186, Trp229) and has substantial interactions with, the backbones of several less well-conserved residues. On the basis of, this structure, we designed substituted DHBNH derivatives that interact, with the NNRTI-binding pocket. These compounds inhibit both the polymerase, and RNH activities of RT.
About this Structure
2I5J 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
HIV-1 reverse transcriptase structure with RNase H inhibitor dihydroxy benzoyl naphthyl hydrazone bound at a novel site., Himmel DM, Sarafianos SG, Dharmasena S, Hossain MM, McCoy-Simandle K, Ilina T, Clark AD Jr, Knight JL, Julias JG, Clark PK, Krogh-Jespersen K, Levy RM, Hughes SH, Parniak MA, Arnold E, ACS Chem Biol. 2006 Dec 20;1(11):702-12. PMID:17184135
Page seeded by OCA on Wed Jan 23 15:30:46 2008
Categories: Human immunodeficiency virus 1 | Protein complex | RNA-directed DNA polymerase | Arnold, E. | Himmel, D.M. | Knight, J.L. | Levy, R.M. | Sarafianos, S.G. | GLC | K05 | MG | SUC | Aids | Crystal structure | Drug resistance | Hiv | Protein-inhibitor complex | Reverse transcriptase | Rnase h inhibitor | Rnhi | Rt | Structure-based drug design
