2WE6

Crystal Structure of Plasmodium falciparum Ubiquitin Carboxyl- terminal Hydrolase 3 (UCHL3)

2WE6 の概要

• エントリーDOI: 10.2210/pdb2we6/pdb
• 関連するPDBエントリー: 2WDT
• 分子名称: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE L3 (2 entities in total)
• 機能のキーワード: cystein proteinase, deneddylating enzyme, ubiquitin isopeptidase, deubiquitinating enzyme, hydrolase, peptidase_c12, uch-l superfamily
• 由来する生物種: PLASMODIUM FALCIPARUM (MALARIA PARASITE)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53860.64

構造登録者

Weihofen, W.A.,Artavanis-Tsakonas, K.,Gaudet, R.,Ploegh, H.L. (登録日: 2009-03-27, 公開日: 2009-12-29, 最終更新日: 2023-12-13)

主引用文献

Artavanis-Tsakonas, K.,Weihofen, W.A.,Antos, J.M.,Coleman, B.I.,Comeaux, C.A.,Duraisingh, M.T.,Gaudet, R.,Ploegh, H.L.
Characterization and Structural Studies of the Plasmodium Falciparum Ubiquitin and Nedd8 Hydrolase Uchl3.
J.Biol.Chem., 285:6857-, 2010

PubMed Abstract: Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed the identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected.

PubMed: 20042598
DOI: 10.1074/JBC.M109.072405

実験手法

X-RAY DIFFRACTION (2.42 Å)