2i5j

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[[Image:2i5j.gif|left|200px]]
[[Image:2i5j.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2i5j |SIZE=350|CAPTION= <scene name='initialview01'>2i5j</scene>, resolution 3.150&Aring;
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The line below this paragraph, containing "STRUCTURE_2i5j", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=K05:(E)-3,4-DIHYDROXY-N&#39;-[(2-METHOXYNAPHTHALEN-1-YL)METHYLENE]BENZOHYDRAZIDE'>K05</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|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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-->
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|DOMAIN=
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{{STRUCTURE_2i5j| PDB=2i5j | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i5j OCA], [http://www.ebi.ac.uk/pdbsum/2i5j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2i5j RCSB]</span>
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}}
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'''Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor'''
'''Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor'''
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[[Category: Levy, R M.]]
[[Category: Levy, R M.]]
[[Category: Sarafianos, S G.]]
[[Category: Sarafianos, S G.]]
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[[Category: aid]]
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[[Category: Aid]]
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[[Category: crystal structure]]
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[[Category: Crystal structure]]
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[[Category: drug resistance]]
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[[Category: Drug resistance]]
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[[Category: hiv]]
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[[Category: Hiv]]
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[[Category: protein-inhibitor complex]]
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[[Category: Protein-inhibitor complex]]
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[[Category: reverse transcriptase]]
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[[Category: Reverse transcriptase]]
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[[Category: rnase h inhibitor]]
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[[Category: Rnase h inhibitor]]
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[[Category: rnhi]]
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[[Category: Rnhi]]
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[[Category: rt]]
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[[Category: Rt]]
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[[Category: structure-based drug design]]
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[[Category: Structure-based drug design]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:05:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:39:59 2008''
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Revision as of 04:05, 4 May 2008

Image:2i5j.gif

Template:STRUCTURE 2i5j

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 May 4 07:05:49 2008

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