7PJE

Inhibiting parasite proliferation using a rationally designed anti-tubulin agent

7PJE の概要

• エントリーDOI: 10.2210/pdb7pje/pdb
• 分子名称: Tubulin alpha chain, Tubulin beta chain, Darpin D1, ... (6 entities in total)
• 機能のキーワード: tubulin, microtubules, protozoa, apicomplexa, structural protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 233550.35

構造登録者

Sharma, A.,Gaillard, N.,Ehrhard, V.A.,Steinmetz, M.O. (登録日: 2021-08-24, 公開日: 2021-09-22, 最終更新日: 2024-01-31)

主引用文献

Gaillard, N.,Sharma, A.,Abbaali, I.,Liu, T.,Shilliday, F.,Cook, A.D.,Ehrhard, V.,Bangera, M.,Roberts, A.J.,Moores, C.A.,Morrissette, N.,Steinmetz, M.O.
Inhibiting parasite proliferation using a rationally designed anti-tubulin agent.
Embo Mol Med, 13:e13818-e13818, 2021

PubMed Abstract: Infectious diseases caused by apicomplexan parasites remain a global public health threat. The presence of multiple ligand-binding sites in tubulin makes this protein an attractive target for anti-parasite drug discovery. However, despite remarkable successes as anti-cancer agents, the rational development of protozoan parasite-specific tubulin drugs has been hindered by a lack of structural and biochemical information on protozoan tubulins. Here, we present atomic structures for a protozoan tubulin and microtubule and delineate the architectures of apicomplexan tubulin drug-binding sites. Based on this information, we rationally designed the parasite-specific tubulin inhibitor parabulin and show that it inhibits growth of parasites while displaying no effects on human cells. Our work presents for the first time the rational design of a species-specific tubulin drug providing a framework to exploit structural differences between human and protozoa tubulin variants enabling the development of much-needed, novel parasite inhibitors.

PubMed: 34661376
DOI: 10.15252/emmm.202013818

実験手法

X-RAY DIFFRACTION (1.75 Å)