6p2g

Structure of HIV-1 Reverse Transcriptase (RT) in complex with dsDNA and D-ddCTP

spinqualitylabelsall models 6p2g, resolution 2.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6p2g is a 4 chain structure with sequence from HIV-1 M:B_HXB2R and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.99Å Ligands: DCT, DDG, G47, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Reverse transcriptase 3D structures

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