2WDT

Crystal structure of Plasmodium falciparum UCHL3 in complex with the suicide inhibitor UbVME

2WDT の概要

• エントリーDOI: 10.2210/pdb2wdt/pdb
• 関連するPDBエントリー: 1C3T 1D3Z 1F9J 1FXT 1G6J 1GJZ 1NBF 1OGW 1Q5W 1S1Q 1SIF 1TBE 1UBI 1UBQ 1XD3 1XQQ 1YX5 1YX6 1ZGU 2AYO 2BGF 2G45 2GBJ 2GBK 2GBM 2GBN 2J7Q 2JF5 2W9N
• 分子名称: UBIQUITIN CARBOXYL-TERMINAL HYDROLASE L3, UBIQUITIN, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase-protein binding complex, enzyme-ligand complex, ubiquitin isopeptidase, uch-l superfamily, cystein proteinase, peptidase_c12, hydrolase, hydrolase/protein binding
• 由来する生物種: PLASMODIUM FALCIPARUM (MALARIA PARASITE); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71169.37

構造登録者

Weihofen, W.A.,Artavanis-Tsakonas, K.,Gaudet, R.,Ploegh, H.L. (登録日: 2009-03-26, 公開日: 2009-12-29, 最終更新日: 2024-11-20)

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 (2.3 Å)