7SO4

Crystal Structure of HIV-1 Y181C mutant Reverse Transcriptase in Complex with 5-(2-(2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)-7-fluoro-2-naphthonitrile (JLJ635), a Non-nucleoside Inhibitor

7SO4 の概要

• エントリーDOI: 10.2210/pdb7so4/pdb
• 分子名称: Reverse transcriptase/ribonuclease H, p51 RT, 5-{2-[2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]phenoxy}-7-fluoronaphthalene-2-carbonitrile, ... (5 entities in total)
• 機能のキーワード: nnrtis, hiv-1, drug design, transferase, hydrolase, transferase-viral protein complex, transferase/viral protein
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate BH10); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114482.15

構造登録者

Bertoletti, N.,Anderson, K.S.,Cisneros Trigo, J.A.,Jorgensen, W.L.,Frey, K.M.,Chan, A.H. (登録日: 2021-10-29, 公開日: 2022-03-16, 最終更新日: 2023-10-18)

主引用文献

Frey, K.M.,Bertoletti, N.,Chan, A.H.,Ippolito, J.A.,Bollini, M.,Spasov, K.A.,Jorgensen, W.L.,Anderson, K.S.
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.
Front Mol Biosci, 9:805187-805187, 2022

PubMed Abstract: Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT crystal structure complex that was solved with non-nucleoside reverse transcriptase inhibitor nevirapine. The release of this structure opened opportunities for designing many families of non-nucleoside reverse transcriptase inhibitors (NNRTIs). In paying tribute to the first RT-nevirapine structure, we have developed several compound classes targeting the non-nucleoside inhibitor binding pocket of HIV RT. Extensive analysis of crystal structures of RT in complex with the compounds informed iterations of structure-based drug design. Structures of seven additional complexes were determined and analyzed to summarize key interactions with residues in the non-nucleoside inhibitor binding pocket (NNIBP) of RT. Additional insights comparing structures with antiviral data and results from molecular dynamics simulations elucidate key interactions and dynamics between the nucleotide and non-nucleoside binding sites.

PubMed: 35237658
DOI: 10.3389/fmolb.2022.805187

実験手法

X-RAY DIFFRACTION (2.95 Å)