Journal article
Structural Understanding of the Glutathione-dependent Reduction Mechanism of Glutathionyl-Hydroquinone Reductases
The Journal of biological chemistry, Vol.287(43), pp.35838-35848
10/19/2012
Handle:
https://hdl.handle.net/2376/104426
PMCID: PMC3476253
PMID: 22955277
Abstract
Background:
Glutathionyl-hydroquinone reductases (GS-HQRs) are a newly recognized and widely distributed class of GSTs using GSH to reduce GS-hydroquinones to hydroquinone.
Results:
Three Tyr and a Cys within the active site contribute to catalytic activity.
Conclusion:
The residues constituting the active site and dimer interface are conserved among GS-HQRs.
Significance:
This is a thorough characterization of GS-HQRs, providing the structural link to enzymatic activity.
Glutathionyl-hydroquinone reductases (GS- HQRs) are a newly identified group of glutathione transferases, and they are widely distributed in bacteria, halobacteria, fungi, and plants. GS-HQRs catalyze glutathione (GSH)-dependent reduction of glutathionyl-hydroquinones (GS-hydroquinones) to hydroquinones. GS-hydroquinones can be spontaneously formed from benzoquinones reacting with reduced GSH via Michael addition, and GS-HQRs convert the conjugates to hydroquinones. In this report we have determined the structures of two bacterial GS-HQRs, PcpF of
Sphingobium chlorophenolicum
and YqjG of
Escherichia coli
. The two structures and the previously reported structure of a fungal GS-HQR shared many features and displayed complete conservation for all the critical residues. Furthermore, we obtained the binary complex structures with GS-menadione, which in its reduced form, GS-menadiol, is a substrate. The structure revealed a large H-site that could accommodate various substituted hydroquinones and a hydrogen network of three Tyr residues that could provide the proton for reductive deglutathionylation. Mutation of the Tyr residues and the position of two GSH molecules confirmed the proposed mechanism of GS-HQRs. The conservation of GS-HQRs across bacteria, halobacteria, fungi, and plants potentiates the physiological role of these enzymes in quinone metabolism.
Metrics
3 Record Views
Details
- Title
- Structural Understanding of the Glutathione-dependent Reduction Mechanism of Glutathionyl-Hydroquinone Reductases
- Creators
- Abigail R Green - From theRobert P Hayes - theLuying Xun - From theChulHee Kang - From the
- Publication Details
- The Journal of biological chemistry, Vol.287(43), pp.35838-35848
- Academic Unit
- Chemistry, Department of; Molecular Biosciences, School of
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Identifiers
- 99900546684601842
- Language
- English
- Resource Type
- Journal article