7OUT

HIV-1 REVERSE TRANSCRIPTASE COMPLEX WITH DNA AND INHIBITOR RMC-264

Summary for 7OUT

• Entry DOI: 10.2210/pdb7out/pdb
• Related: 7OT6 7OTA 7OTK 7OTN 7OTX 7OTZ
• Descriptor: Reverse transcriptase/ribonuclease H, DNA (5'-D(P*GP*GP*TP*CP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*G)-3'), DNA (5'-D(*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*(MRG)P*CP*GP*CP*CP*(DDG))-3'), ... (7 entities in total)
• Functional Keywords: reverse transcriptase, rt inhibitor complex, acyclic nucleoside phosphonate analog, rt-dna complex, transferase
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1); More
• Total number of polymer chains: 8
• Total formula weight: 258208.66

Authors

Martinez, S.E.,Singh, A.K.,Gu, W.,Das, K. (deposition date: 2021-06-13, release date: 2021-12-08, Last modification date: 2024-01-31)

Primary citation

Gu, W.,Martinez, S.,Singh, A.K.,Nguyen, H.,Rozenski, J.,Schols, D.,Herdewijn, P.,Das, K.,De Jonghe, S.
Exploring the dNTP -binding site of HIV-1 reverse transcriptase for inhibitor design.
Eur.J.Med.Chem., 225:113785-113785, 2021

PubMed Abstract: HIV-1 reverse transcriptase (RT) plays a central role in the viral life cycle, and roughly half of the FDA-approved anti-HIV drugs are targeting RT. Nucleoside analogs (NRTIs) require cellular phosphorylation for binding to RT, and to bypass this rate-limiting path, we designed a new series of acyclic nucleoside phosphonate analogs as nucleoside triphosphate mimics, aiming at the chelation of the catalytic Mg ions via a phosphonate and/or a carboxylic acid group. Novel synthetic procedures were developed to access these nucleoside phosphonate analogs. X-ray structures in complex with HIV-1 RT/dsDNA demonstrated that their binding modes are distinct from that of our previously reported compound series. The impact of chain length, chirality and linker atom have been discussed. The detailed structural understanding of these new compounds provides opportunities for designing new class of HIV-1 RT inhibitors.

PubMed: 34425311
DOI: 10.1016/j.ejmech.2021.113785

Experimental method

X-RAY DIFFRACTION (3.2 Å)