5LX0

Cys-Gly dipeptidase GliJ (space group P3221)

5LX0 の概要

• エントリーDOI: 10.2210/pdb5lx0/pdb
• 関連するPDBエントリー: 5LWZ
• 分子名称: Dipeptidase, FE (III) ION (3 entities in total)
• 機能のキーワード: carboxypeptidase, dipeptidase, gliotoxin biosynthesis, hydrolase
• 由来する生物種: Aspergillus fumigatus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44990.57

構造登録者

Huber, E.M.,Groll, M. (登録日: 2016-09-19, 公開日: 2017-05-31, 最終更新日: 2024-11-20)

主引用文献

Marion, A.,Groll, M.,Scharf, D.H.,Scherlach, K.,Glaser, M.,Sievers, H.,Schuster, M.,Hertweck, C.,Brakhage, A.A.,Antes, I.,Huber, E.M.
Gliotoxin Biosynthesis: Structure, Mechanism, and Metal Promiscuity of Carboxypeptidase GliJ.
ACS Chem. Biol., 12:1874-1882, 2017

PubMed Abstract: The formation of glutathione (GSH) conjugates, best known from the detoxification of xenobiotics, is a widespread strategy to incorporate sulfur into biomolecules. The biosynthesis of gliotoxin, a virulence factor of the human pathogenic fungus Aspergillus fumigatus, involves attachment of two GSH molecules and their sequential decomposition to yield two reactive thiol groups. The degradation of the GSH moieties requires the activity of the Cys-Gly carboxypeptidase GliJ, for which we describe the X-ray structure here. The enzyme forms a homodimer with each monomer comprising one active site. Two metal ions are present per proteolytic center, thus assigning GliJ to the diverse family of dinuclear metallohydrolases. Depending on availability, Zn, Fe, Fe, Mn, Cu, Co, or Ni ions are accepted as cofactors. Despite this high metal promiscuity, a preference for zinc versus iron and manganese was noted. Mutagenesis experiments revealed details of metal coordination, and molecular modeling delivered insights into substrate recognition and processing by GliJ. The latter results suggest a reaction mechanism in which the two scissile peptide bonds of one gliotoxin precursor molecule are hydrolyzed sequentially and in a given order.

PubMed: 28525266
DOI: 10.1021/acschembio.6b00847

実験手法

X-RAY DIFFRACTION (2.4 Å)