Acid-base catalysis in the mechanism of thioredoxin reductase from Drosophila melanogaster

Biochemistry
Hsin-Hung HuangCharles H Williams

Abstract

Thioredoxin reductase (TrxR) catalyzes the reduction of thioredoxin (Trx) by NADPH. Like other members of the pyridine nucleotide-disulfide oxidoreductase enzyme family, the enzyme from Drosophila melanogaster is a homodimer, and each catalytically active unit consists of three redox centers: FAD and an N-terminal Cys-57/Cys-62 redox-active disulfide from one monomer and a Cys-489'/Cys-490' C-terminal redox-active disulfide from the second monomer. Because dipteran insects such as D. melanogaster lack glutathione reductase, thioredoxin reductase (DmTrxR) is particularly important; in addition to its normal functions, it also reduces GSSG for antioxidant protection. DmTrxR, used as a model for the enzyme from the malaria vector, Anopheles gambiae, has been shown to cycle in catalysis between the two-electron and four-electron reduced states, EH2 and EH4 [Bauer, H. et al. (2003) J. Biol. Chem. 278, 33020-33028]. His-464' acts as an acid-base catalyst of the dithiol-disulfide interchange reactions required in catalysis. The H464'Q enzyme has only 2% of the wild-type activity, emphasizing the importance of this residue. The pH dependence of Vmax for wild-type DmTrxR has pKa values of 6.4 and 9.3 on the DmTrxR-DmTrx-2 complex, where...Continue Reading

References

Jun 5, 1987·Journal of Molecular Biology·P A Karplus, G E Schulz
Aug 20, 1985·Journal of Molecular Biology·H Tsukada, D M Blow
Nov 5, 2003·Medicinal Research Reviews·Stephan GromerKatja Becker
Dec 24, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Walter H WatsonJames P Kehrer
Jun 16, 2005·Cancer Letters·Phuongmai NguyenDavid Gius
Sep 5, 2006·The Journal of Biological Chemistry·Paul J McMillanSylke Müller
Dec 19, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Carsten BerndtArne Holmgren

❮ Previous
Next ❯

Citations

Apr 17, 2010·Amino Acids·Robert J Hondal, Erik L Ruggles
Nov 7, 2008·Biochemistry·Brian M LaceyRobert J Hondal
Jul 28, 2010·The Journal of Biological Chemistry·Francesco AngelucciAndrea Bellelli
Jan 28, 2009·The Journal of Biological Chemistry·Ikuo SatoNaoki Takaya
Dec 15, 2011·Journal of Inorganic Biochemistry·Fulvio SaccocciaAndrea Bellelli
Nov 8, 2011·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Prakash M Gopalakrishnan Nair, Jinhee Choi
Apr 20, 2010·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Haifang YangBaohua Xu
Sep 23, 2020·International Journal of Biological Macromolecules·Nikhilesh JoardarSanti P Sinha Babu
Sep 3, 2010·The Journal of Organic Chemistry·Daniel SteinmannWillem H Koppenol

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.