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Structure of human constitutive 20S proteasome complexed with the inhibitor TDI-8304

ABSTRACT:

SUBMITTER: Hao-Chi Hsu

PROVIDER: EMPIAR-11842 | biostudies-other |

REPOSITORIES: biostudies-other

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Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors.

Hsu Hao-Chi HC Li Daqiang D Zhan Wenhu W Ye Jianxiang J Liu Yi Jing YJ Leung Annie A Qin Junling J Crespo Benigno B Gamo Francisco-Javier FJ Zhang Hao H Cui Liwang L Roth Alison A Kirkman Laura A LA Li Huilin H Lin Gang G

Nature communications 20231214 1

The proteasome of the malaria parasite Plasmodium falciparum (Pf20S) is an advantageous drug target because its inhibition kills P. falciparum in multiple stages of its life cycle and synergizes with artemisinins. We recently developed a macrocyclic peptide, TDI-8304, that is highly selective for Pf20S over human proteasomes and is potent in vitro and in vivo against P. falciparum. A mutation in the Pf20S β6 subunit, A117D, confers resistance to TDI-8304, yet enhances both enzyme inhibition and ...[more]

PMID: 38097652

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