7MIQ

Crystal structure of a Glutathione S-transferase class Gtt2 of Vibrio parahaemolyticus (VpGSTT2)

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7MIQ の概要

• エントリーDOI: 10.2210/pdb7miq/pdb
• 分子名称: Glutathione S-transferase, DI(HYDROXYETHYL)ETHER, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: gst folding, thioredoxin domain, transferase, gtt2 class
• 由来する生物種: Vibrio parahaemolyticus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48468.51

構造登録者

Valenzuela-Chavira, I.,Serrano-Posada, H.,Lopez-Zavala, A.A.,Garcia-Orozco, K.D.,Sotelo-Mundo, R.R. (登録日: 2021-04-17, 公開日: 2021-07-07, 最終更新日: 2023-10-18)

主引用文献

Valenzuela-Chavira, I.,Corona-Martinez, D.O.,Garcia-Orozco, K.D.,Beltran-Torres, M.,Sanchez-Lopez, F.,Arvizu-Flores, A.A.,Sugich-Miranda, R.,Lopez-Zavala, A.A.,Robles-Zepeda, R.E.,Islas-Osuna, M.A.,Ochoa-Leyva, A.,Toney, M.D.,Serrano-Posada, H.,Sotelo-Mundo, R.R.
A Novel Glutathione S -Transferase Gtt2 Class (VpGSTT2) Is Found in the Genome of the AHPND/EMS Vibrio parahaemolyticus Shrimp Pathogen.
Toxins, 13:-, 2021

PubMed Abstract: Glutathione S-transferases are a family of detoxifying enzymes that catalyze the conjugation of reduced glutathione (GSH) with different xenobiotic compounds using either Ser, Tyr, or Cys as a primary catalytic residue. We identified a novel GST in the genome of the shrimp pathogen FIM- S1708, a bacterial strain associated with Acute Hepatopancreatic Necrosis Disease (AHPND)/Early Mortality Syndrome (EMS) in cultured shrimp. This new GST class was named Gtt2. It has an atypical catalytic mechanism in which a water molecule instead of Ser, Tyr, or Cys activates the sulfhydryl group of GSH. The biochemical properties of Gtt2 from (VpGSTT2) were characterized using kinetic and crystallographic methods. Recombinant VpGSTT2 was enzymatically active using GSH and CDNB as substrates, with a specific activity of 5.7 units/mg. Low affinity for substrates was demonstrated using both Michaelis-Menten kinetics and isothermal titration calorimetry. The crystal structure showed a canonical two-domain structure comprising a glutathione binding G-domain and a hydrophobic ligand H domain. A water molecule was hydrogen-bonded to residues Thr9 and Ser 11, as reported for the yeast Gtt2, suggesting a primary role in the reaction. Molecular docking showed that GSH could bind at the G-site in the vicinity of Ser11. G-site mutationsT9A and S11A were analyzed. S11A retained 30% activity, while T9A/S11A showed no detectable activity. VpGSTT2 was the first bacterial Gtt2 characterized, in which residues Ser11 and Thr9 coordinated a water molecule as part of a catalytic mechanism that was characteristic of yeast GTT2. The GTT2 family has been shown to provide protection against metal toxicity; in some cases, excess heavy metals appear in shrimp ponds presenting AHPND/EMS. Further studies may address whether GTT2 in pathogenic strains may provide a competitive advantage as a novel detoxification mechanism.

PubMed: 34564668
DOI: 10.3390/toxins13090664

実験手法

X-RAY DIFFRACTION (1.92 Å)