3QCP

QSOX from Trypanosoma brucei

3QCP の概要

• エントリーDOI: 10.2210/pdb3qcp/pdb
• 関連するPDBエントリー: 3QD9
• 分子名称: QSOX from Trypanosoma brucei (TbQSOX), FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: erv fold, thioredoxin fold, sulfhydryl oxidase, oxidoreductase
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53027.01

構造登録者

Alon, A.,Fass, D. (登録日: 2011-01-17, 公開日: 2012-05-30, 最終更新日: 2024-11-27)

主引用文献

Alon, A.,Grossman, I.,Gat, Y.,Kodali, V.K.,DiMaio, F.,Mehlman, T.,Haran, G.,Baker, D.,Thorpe, C.,Fass, D.
The dynamic disulphide relay of quiescin sulphydryl oxidase.
Nature, 488:414-418, 2012

PubMed Abstract: Protein stability, assembly, localization and regulation often depend on the formation of disulphide crosslinks between cysteine side chains. Enzymes known as sulphydryl oxidases catalyse de novo disulphide formation and initiate intra- and intermolecular dithiol/disulphide relays to deliver the disulphides to substrate proteins. Quiescin sulphydryl oxidase (QSOX) is a unique, multi-domain disulphide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention owing to its overproduction in tumours. In addition to its physiological importance, QSOX is a mechanistically intriguing enzyme, encompassing functions typically carried out by a series of proteins in other disulphide-formation pathways. How disulphides are relayed through the multiple redox-active sites of QSOX and whether there is a functional benefit to concatenating these sites on a single polypeptide are open questions. Here we present the first crystal structure of an intact QSOX enzyme, derived from a trypanosome parasite. Notably, sequential sites in the disulphide relay were found more than 40 Å apart in this structure, too far for direct disulphide transfer. To resolve this puzzle, we trapped and crystallized an intermediate in the disulphide hand-off, which showed a 165° domain rotation relative to the original structure, bringing the two active sites within disulphide-bonding distance. The comparable structure of a mammalian QSOX enzyme, also presented here, shows further biochemical features that facilitate disulphide transfer in metazoan orthologues. Finally, we quantified the contribution of concatenation to QSOX activity, providing general lessons for the understanding of multi-domain enzymes and the design of new catalytic relays.

PubMed: 22801504
DOI: 10.1038/nature11267

実験手法

X-RAY DIFFRACTION (2.3 Å)