A "Seleno Effect" Differentiates the Roles of Redox Active Cysteine Residues in Plasmodium falciparum Thioredoxin Reductase

Biochemistry
John P O'KeefeRobert J Hondal

Abstract

Here, we introduce the concept of the "seleno effect" in the study of oxidoreductases that catalyze thiol/disulfide exchange reactions. In these reactions, selenium can replace sulfur as a nucleophile, electrophile, or leaving group, and the resulting change in rate (the seleno effect) is defined as kS/ kSe. In solution, selenium accelerates the rate of thiol/disulfide exchange regardless of its chemical role (e.g., nucleophile or electrophile). Here we show that this is not the case for enzyme catalyzed reactions and that the magnitude of the seleno effect can differentiate the role of each sulfur atom of a disulfide bond between that of an electrophile or leaving group. We used selenium for sulfur substitution to study the thiol/disulfide exchange step that occurs between the N-terminal redox center and the C-terminal disulfide-containing β-hairpin motif of Plasmodium falciparum thioredoxin reductase (PfTrxR), which has the sequence Gly-Cys535-Gly-Gly-Gly-Lys-Cys540-Gly. We assayed a truncated PfTrxR enzyme missing this C-terminal tail for disulfide-reductase activity using synthetic peptide substrates in which either Cys535 or Cys540 was replaced with selenocysteine (Sec). The results show that substitution of Cys535 with Se...Continue Reading

References

Jan 1, 1989·Advances in Enzymology and Related Areas of Molecular Biology·P A Frey
Oct 1, 1967·Archives of Biochemistry and Biophysics·R E Huber, R S Criddle
Jan 1, 1980·Annual Review of Biochemistry·J R Knowles
Jan 1, 1982·Methods in Enzymology·F EcksteinB A Connolly
Apr 13, 1993·Biochemistry·I M BellD Hilvert
Jun 13, 1998·Biochemistry·H J SchirraR Glockshuber
Nov 25, 1998·Protein Science : a Publication of the Protein Society·T C EvansM Q Xu
Oct 3, 2000·The Journal of Biological Chemistry·S M KanzokK Becker
Jun 27, 1997·The Journal of Organic Chemistry·Yongxin HanGeorge Barany
Apr 1, 1958·Archives of Biochemistry and Biophysics·G L ELLMAN
Mar 31, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·K DarlakG Barany
Jan 24, 2006·Nucleic Acids Research·Alexey V LobanovVadim N Gladyshev
Apr 19, 2006·Biochemistry·Brian EckenrothRobert J Hondal
Nov 7, 2008·Biochemistry·Brian M LaceyRobert J Hondal
Sep 3, 2010·The Journal of Organic Chemistry·Daniel SteinmannWillem H Koppenol
Mar 9, 2011·Biochemistry·Santhosh SivaramakrishnanPaul R Ortiz de Montellano
Aug 1, 1995·Journal of the American Chemical Society·J M MessmoreR T Raines
Nov 6, 2012·Antioxidants & Redox Signaling·Robert J HondalVadim N Gladyshev
Jul 13, 2013·Journal of Molecular Biology·Karin Fritz-WolfKatja Becker
Dec 24, 2013·Biochemistry·Jacob D GrahamKim D Collins
Dec 17, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Stevenson Flemer
Mar 8, 2016·ACS Chemical Biology·Hans J Reich, Robert J Hondal

❮ Previous
Next ❯

Citations

Jul 28, 2018·Protein Science : a Publication of the Protein Society·Drew R Barber, Robert J Hondal
Nov 28, 2019·Biochemistry·Brandon L GreeneDaniel G Nocera
Nov 28, 2019·Chemical Reviews·Robert E Thompson, Tom W Muir

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.