7D66

Crystal structure of retroviral protease-like domain of Ddi1 from Toxoplasma gondii

7D66 の概要

• エントリーDOI: 10.2210/pdb7d66/pdb
• 分子名称: Ubiquitin family protein, GLYCEROL (3 entities in total)
• 機能のキーワード: retroviral protease, hydrolase
• 由来する生物種: Toxoplasma gondii GT1
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 175076.26

構造登録者

Biswas, I.B.,Killivalavan, A.K.,Suguna, K.S. (登録日: 2020-09-29, 公開日: 2022-02-09, 最終更新日: 2023-11-29)

主引用文献

Asaithambi, K.,Biswas, I.,Suguna, K.
Structural and functional insights into the DNA damage-inducible protein 1 (Ddi1) from protozoa.
Curr Res Struct Biol, 4:175-191, 2022

PubMed Abstract: Ddi1 is a multidomain protein that belongs to the ubiquitin receptor family of proteins. The Ddi1 proteins contain a highly conserved retroviral protease (RVP)-like domain along with other domains. The severity of opportunistic infections, caused by parasitic protozoa in AIDS patients, was found to decline when HIV protease inhibitors were used in antiretroviral therapy. Parasite growth was shown to be suppressed by a few of the inhibitors targeting Ddi1 present in these parasites. In this study, the binding of HIV protease inhibitors to the RVP domain of Ddi1 from and ; and the binding of ubiquitin to the ubiquitin-associated domain of Ddi1 from these two parasites were established using Biolayer Interferometry. The crystal structures of the RVP domains of Ddi1 from and were determined; they form homodimers similar to those observed in HIV protease and the reported structures of the same domain from , and humans. The native form of the domain showed an open dimeric structure and a normal mode analysis revealed that it can take up a closed conformation resulting from relative movements of the subunits. Based on the crystal structure of the RVP domain of Ddi1 from , a seven residue peptide inhibitor was designed and it was shown to bind to the RVP domain of Ddi1 from by Biolayer Interferometry. This peptide was modified using computational methods and was shown to have a better affinity than the initial peptide.

PubMed: 35677776
DOI: 10.1016/j.crstbi.2022.05.003

実験手法

X-RAY DIFFRACTION (2.126 Å)