Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases

Alphey MS, König J, Fairlamb AH (2008)
The Biochemical Journal 414(3): 375-381.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ;
Abstract / Bemerkung
TbTDPX (Trypanosoma brucei tryparedoxin-dependent peroxidase) is a genetically validated drug target in the fight against African sleeping sickness. Despite its similarity to members of the GPX (glutathione peroxidase) family, TbTDPX2 is functional as a monomer, lacks a selenocysteine residue and relies instead on peroxidatic and resolving cysteine residues for catalysis and uses tryparedoxin rather than glutathione as electron donor. Kinetic studies indicate a saturable Ping Pong mechanism, unlike selenium-dependent GPXs, which display infinite K(m) and V(max) values. The structure of the reduced enzyme at 2.1 A (0.21 nm) resolution reveals that the catalytic thiol groups are widely separated [19 A (0.19 nm)] and thus unable to form a disulphide bond without a large conformational change in the secondary-structure architecture, as reported for certain plant GPXs. A model of the oxidized enzyme structure is presented and the implications for small-molecule inhibition are discussed.
Erscheinungsjahr
Zeitschriftentitel
The Biochemical Journal
Band
414
Ausgabe
3
Seite(n)
375-381
ISSN
eISSN
PUB-ID

Zitieren

Alphey MS, König J, Fairlamb AH. Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases. The Biochemical Journal. 2008;414(3):375-381.
Alphey, M. S., König, J., & Fairlamb, A. H. (2008). Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases. The Biochemical Journal, 414(3), 375-381. doi:10.1042/BJ20080889
Alphey, M. S., König, J., and Fairlamb, A. H. (2008). Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases. The Biochemical Journal 414, 375-381.
Alphey, M.S., König, J., & Fairlamb, A.H., 2008. Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases. The Biochemical Journal, 414(3), p 375-381.
M.S. Alphey, J. König, and A.H. Fairlamb, “Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases”, The Biochemical Journal, vol. 414, 2008, pp. 375-381.
Alphey, M.S., König, J., Fairlamb, A.H.: Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases. The Biochemical Journal. 414, 375-381 (2008).
Alphey, Magnus S, König, Janine, and Fairlamb, Alan H. “Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases”. The Biochemical Journal 414.3 (2008): 375-381.

12 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

A Comparative In Silico Study of the Antioxidant Defense Gene Repertoire of Distinct Lifestyle Trypanosomatid Species.
Beltrame-Botelho IT, Talavera-López C, Andersson B, Grisard EC, Stoco PH., Evol Bioinform Online 12(), 2016
PMID: 27840574
The Corynebacterium glutamicum mycothiol peroxidase is a reactive oxygen species-scavenging enzyme that shows promiscuity in thiol redox control.
Pedre B, Van Molle I, Villadangos AF, Wahni K, Vertommen D, Turell L, Erdogan H, Mateos LM, Messens J., Mol Microbiol 96(6), 2015
PMID: 25766783
Structural insights into the enzymes of the trypanothione pathway: targets for antileishmaniasis drugs.
Colotti G, Baiocco P, Fiorillo A, Boffi A, Poser E, Chiaro FD, Ilari A., Future Med Chem 5(15), 2013
PMID: 24144416
Peroxiredoxins in parasites.
Gretes MC, Poole LB, Karplus PA., Antioxid Redox Signal 17(4), 2012
PMID: 22098136
Hydroperoxide and peroxynitrite reductase activity of poplar thioredoxin-dependent glutathione peroxidase 5: kinetics, catalytic mechanism and oxidative inactivation.
Selles B, Hugo M, Trujillo M, Srivastava V, Wingsle G, Jacquot JP, Radi R, Rouhier N., Biochem J 442(2), 2012
PMID: 22122405
Polyamine metabolism in Leishmania: from arginine to trypanothione.
Colotti G, Ilari A., Amino Acids 40(2), 2011
PMID: 20512387
A comparison of thiol peroxidase mechanisms.
Flohé L, Toppo S, Cozza G, Ursini F., Antioxid Redox Signal 15(3), 2011
PMID: 20649470
Antitumor quinol PMX464 is a cytocidal anti-trypanosomal inhibitor targeting trypanothione metabolism.
König J, Wyllie S, Wells G, Stevens MF, Wyatt PG, Fairlamb AH., J Biol Chem 286(10), 2011
PMID: 21212280
A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage.
Diechtierow M, Krauth-Siegel RL., Free Radic Biol Med 51(4), 2011
PMID: 21640819
Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I).
Patel S, Hussain S, Harris R, Sardiwal S, Kelly JM, Wilkinson SR, Driscoll PC, Djordjevic S., Biochem J 425(3), 2010
PMID: 19886864

28 References

Daten bereitgestellt von Europe PubMed Central.

Kinetoplastids: related protozoan pathogens, different diseases.
Stuart K, Brun R, Croft S, Fairlamb A, Gurtler RE, McKerrow J, Reed S, Tarleton R., J. Clin. Invest. 118(4), 2008
PMID: 18382742
Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress.
Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL, Clayton C., Mol. Microbiol. 35(3), 2000
PMID: 10672177
Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome.
Ariyanayagam MR, Oza SL, Guther ML, Fairlamb AH., Biochem. J. 391(Pt 2), 2005
PMID: 16008527
Validation of Trypanosoma brucei trypanothione synthetase as drug target.
Comini MA, Guerrero SA, Haile S, Menge U, Lunsdorf H, Flohe L., Free Radic. Biol. Med. 36(10), 2004
PMID: 15110394
A second class of peroxidases linked to the trypanothione metabolism.
Hillebrand H, Schmidt A, Krauth-Siegel RL., J. Biol. Chem. 278(9), 2002
PMID: 12466271
Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei.
Schlecker T, Schmidt A, Dirdjaja N, Voncken F, Clayton C, Krauth-Siegel RL., J. Biol. Chem. 280(15), 2005
PMID: 15664987
Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei.
Schlecker T, Comini MA, Melchers J, Ruppert T, Krauth-Siegel RL., Biochem. J. 405(3), 2007
PMID: 17456049
The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.
Wilkinson SR, Meyer DJ, Taylor MC, Bromley EV, Miles MA, Kelly JM., J. Biol. Chem. 277(19), 2002
PMID: 11842085
Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants
Kabsch W.., 1993
Crystal structures of a poplar thioredoxin peroxidase that exhibits the structure of glutathione peroxidases: insights into redox-driven conformational changes.
Koh CS, Didierjean C, Navrot N, Panjikar S, Mulliert G, Rouhier N, Jacquot JP, Aubry A, Shawkataly O, Corbier C., J. Mol. Biol. 370(3), 2007
PMID: 17531267
MOLREP: an automated program for molecular replacement
Vagin A., Teplyakov A.., 1997
The CCP4 suite: programs for protein crystallography.
Collaborative Computational Project, Number 4., Acta Crystallogr. D Biol. Crystallogr. 50(Pt 5), 1994
PMID: 15299374
Refinement of macromolecular structures by the maximum-likelihood method.
Murshudov GN, Vagin AA, Dodson EJ., Acta Crystallogr. D Biol. Crystallogr. 53(Pt 3), 1997
PMID: 15299926
Coot: model-building tools for molecular graphics.
Emsley P, Cowtan K., Acta Crystallogr. D Biol. Crystallogr. 60(Pt 12 Pt 1), 2004
PMID: 15572765
PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations.
Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA., Nucleic Acids Res. 32(Web Server issue), 2004
PMID: 15215472
Electrostatics of nanosystems: application to microtubules and the ribosome.
Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA., Proc. Natl. Acad. Sci. U.S.A. 98(18), 2001
PMID: 11517324
Mapping the protein universe.
Holm L, Sander C., Science 273(5275), 1996
PMID: 8662544
The refined structure of the selenoenzyme glutathione peroxidase at 0.2-nm resolution.
Epp O, Ladenstein R, Wendel A., Eur. J. Biochem. 133(1), 1983
PMID: 6852035
Where freedom is given, liberties are taken.
Kleywegt GJ, Jones TA., Structure 3(6), 1995
PMID: 8590014
SWISS-MODEL: An automated protein homology-modeling server.
Schwede T, Kopp J, Guex N, Peitsch MC., Nucleic Acids Res. 31(13), 2003
PMID: 12824332
Thioredoxin--a fold for all reasons.
Martin JL., Structure 3(3), 1995
PMID: 7788290
Structural classification of thioredoxin-like fold proteins.
Qi Y, Grishin NV., Proteins 58(2), 2005
PMID: 15558583
Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4).
Scheerer P, Borchert A, Krauss N, Wessner H, Gerth C, Hohne W, Kuhn H., Biochemistry 46(31), 2007
PMID: 17630701

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 18522537
PubMed | Europe PMC

Suchen in

Google Scholar