2i5j

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{{STRUCTURE_2i5j| PDB=2i5j | SCENE= }}
{{STRUCTURE_2i5j| PDB=2i5j | SCENE= }}
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'''Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor'''
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===Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor===
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==Overview==
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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 &gt;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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17184135 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17184135}}
==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/17184135 17184135]
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:[http://www.ncbi.nlm.nih.gov/pubmed/17184135 17184135]
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Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains., Himmel DM, Das K, Clark AD Jr, Hughes SH, Benjahad A, Oumouch S, Guillemont J, Coupa S, Poncelet A, Csoka I, Meyer C, Andries K, Nguyen CH, Grierson DS, Arnold E, J Med Chem. 2005 Dec 1;48(24):7582-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16302798 16302798]
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Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA., Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E, EMBO J. 2001 Mar 15;20(6):1449-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11250910 11250910]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Rt]]
[[Category: Rt]]
[[Category: Structure-based drug design]]
[[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 Sun Jul 27 22:26:52 2008''

Revision as of 19:26, 27 July 2008

Image:2i5j.png

Template:STRUCTURE 2i5j

Crystal structure of HIV-1 reverse transcriptase (RT) in complex with DHBNH, an RNASE H inhibitor

Template:ABSTRACT PUBMED 17184135

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

Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains., Himmel DM, Das K, Clark AD Jr, Hughes SH, Benjahad A, Oumouch S, Guillemont J, Coupa S, Poncelet A, Csoka I, Meyer C, Andries K, Nguyen CH, Grierson DS, Arnold E, J Med Chem. 2005 Dec 1;48(24):7582-91. PMID:16302798

Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA., Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E, EMBO J. 2001 Mar 15;20(6):1449-61. PMID:11250910

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