2i5j
From Proteopedia
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|PDB= 2i5j |SIZE=350|CAPTION= <scene name='initialview01'>2i5j</scene>, resolution 3.150Å | |PDB= 2i5j |SIZE=350|CAPTION= <scene name='initialview01'>2i5j</scene>, resolution 3.150Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=K05:(E)-3,4-DIHYDROXY-N | + | |LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=K05:(E)-3,4-DIHYDROXY-N'-[(2-METHOXYNAPHTHALEN-1-YL)METHYLENE]BENZOHYDRAZIDE'>K05</scene> |
|ACTIVITY= [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] | |ACTIVITY= [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] | ||
|GENE= gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | |GENE= gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
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[[Category: structure-based drug design]] | [[Category: structure-based drug design]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:19:08 2008'' |
Revision as of 13:19, 23 March 2008
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| , resolution 3.150Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | gag (Human immunodeficiency virus 1) | ||||||
| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Sun Mar 23 15:19:08 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 | Aid | Crystal structure | Drug resistance | Hiv | Protein-inhibitor complex | Reverse transcriptase | Rnase h inhibitor | Rnhi | Rt | Structure-based drug design
