4MGV

Crystal structure of FK506 binding domain of plasmodium VIVAX FKBP35 In complex with inhibitor D5

4MGV の概要

• エントリーDOI: 10.2210/pdb4mgv/pdb
• 関連するPDBエントリー: 3IHZ 4ITZ 4J4N 4J4O
• 分子名称: 70 kDa peptidylprolyl isomerase, putative, N'-(1-adamantylcarbonyl)pyridine-4-carbohydrazide (3 entities in total)
• 機能のキーワード: inhibitor, d5, fkbp, fkbp35, isomerase, fk506
• 由来する生物種: Plasmodium vivax
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14271.06

構造登録者

Rajan, S.,Harikishore, A.,Yoon, H.S. (登録日: 2013-08-29, 公開日: 2013-12-04, 最終更新日: 2024-10-16)

主引用文献

Harikishore, A.,Leow, M.L.,Niang, M.,Rajan, S.,Pasunooti, K.K.,Preiser, P.R.,Liu, X.,Yoon, H.S.
Adamantyl derivative as a potent inhibitor of Plasmodium FK506 binding protein 35.
Acs Med.Chem.Lett., 4:1097-1101, 2013

PubMed Abstract: FKBP35, FK506 binding protein family member, in Plasmodium species displays a canonical peptidyl-prolyl isomerase (PPIase) activity and is intricately involved in the protein folding process. Inhibition of PfFKBP35 by FK506 or its analogues were shown to interfere with the in vitro growth of Plasmodium falciparum. In this study, we have synthesized adamantyl derivatives, Supradamal (SRA/4a) and its analogues SRA1/4b and SRA2/4c, which demonstrate submicromolar inhibition of Plasmodium falciparum FK506 binding domain 35 (FKBD35) PPIase activity. SRA and its analogues not only inhibit the in vitro growth of Plasmodium falciparum 3D7 strain but also show stage specific activity by inhibiting the trophozoite stage of the parasite. SRA/4a also inhibits the Plasmodium vivax FKBD35 PPIase activity and our crystal structure of PvFKBD35 in complex with the SRA provides structural insights in achieving selective inhibition against Plasmodium FKBPs.

PubMed: 24900611
DOI: 10.1021/ml400306r

実験手法

X-RAY DIFFRACTION (1.72 Å)