6p2g
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of HIV-1 Reverse Transcriptase (RT) in complex with dsDNA and D-ddCTP== | |
| + | <StructureSection load='6p2g' size='340' side='right'caption='[[6p2g]], [[Resolution|resolution]] 2.99Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6p2g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/HIV-1_M:B_HXB2R HIV-1 M:B_HXB2R] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P2G FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.99Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCT:2,3-DIDEOXYCYTIDINE+5-TRIPHOSPHATE'>DCT</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene>, <scene name='pdbligand=G47:N2-ETHANETHIOL-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>G47</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6p2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p2g OCA], [https://pdbe.org/6p2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p2g RCSB], [https://www.ebi.ac.uk/pdbsum/6p2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p2g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The retrovirus HIV-1 has been a major health issue since its discovery in the early 80s. In 2017, over 37 million people were infected with HIV-1, of which 1.8 million were new infections that year. Currently, the most successful treatment regimen is the highly active anti-retroviral therapy (HAART), which consists of a combination of three to four of the current 26 FDA-approved HIV-1 drugs. Half of these drugs target the reverse transcriptase (RT) enzyme that is essential for viral replication. One class of RT inhibitors are nucleoside reverse transcriptase inhibitors (NRTIs), a crucial component of the HAART therapy. Once incorporated into DNA, NRTIs function as a chain terminator to stop viral DNA replication. Unfortunately, treatment with NRTIs is sometimes linked to toxicity caused by off-target side effects. NRTIs may also target the replicative human mitochondrial DNA polymerase (Pol gamma), causing long-term severe drug toxicity. The goal of this work is to understand the discrimination mechanism of different NRTI analogs by RT. Crystal structures and kinetic experiments are essential for the rational design of new molecules that are able to bind selectively to RT and not Pol gamma. Structural comparison of NRTI-binding modes with both RT and Pol gamma enzymes highlights key amino acids that are responsible for the difference in affinity of these drugs to their targets. Therefore, the long-term goal of this research is to develop safer, next generation therapeutics that can overcome off-target toxicity. This article is protected by copyright. All rights reserved. | ||
| - | + | Structural insights into the recognition of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) by HIV-1 reverse transcriptase: First crystal structures with RT and the active triphosphate forms of lamivudine and emtricitabine.,Bertoletti N, Chan AH, Schinazi RF, Yin YW, Anderson KS Protein Sci. 2019 Jul 13. doi: 10.1002/pro.3681. PMID:31301259<ref>PMID:31301259</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6p2g" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Reverse transcriptase 3D structures|Reverse transcriptase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: HIV-1 M:B_HXB2R]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Anderson KS]] | ||
| + | [[Category: Bertoletti N]] | ||
Current revision
Structure of HIV-1 Reverse Transcriptase (RT) in complex with dsDNA and D-ddCTP
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