Document Detail


Catalytic characteristics of tryparedoxin.
MedLine Citation:
PMID:  9342246     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tryparedoxin, a thioredoxin-related protein from Crithidia fasciculata with a molecular mass of 16 kDa catalyses the reduction of a peroxiredoxin-type peroxidase, Cf21, at the expense of trypanothione [Nogoceke, E., Gommel, D. U., Kiess, M., Kalisz, H. M. & Flohé, L. E. (1997) Biol. Chem. Hoppe-Seyler 378, 827-836]. The kinetic analysis of tryparedoxin revealed an enzyme substitution mechanism. The corresponding molecular event was elucidated to be a reversible oxidoreduction of the disulfide bridge in the thioredoxin-related motif WCPPC. The amino-proximal cysteine residue of this active site was more reactive in S-alkylation experiments than the distal residue. The natural substrates of tryparedoxin, trypanothione and Cf21, could only be substituted by glutathione and glutathione disulfide with considerable loss in activity. The pronounced specificity of tryparedoxin is further accentuated by low limiting Km values for Cf21 and trypanothione (2.2 microM and 130 microM, respectively, as compared to 990 microM for gluthathione disulfide and an infinite value for glutathione). Tryparedoxin can therefore be classified as a trypanothione: peroxiredoxin oxidoreductase. The reduction of tryparedoxin by trypanothione appears to be the rate-limiting step in the trypanothione-dependent hydroperoxide reduction because(a) the regeneration of reduced tryparedoxin from the tryparedoxin-trypanothione complex is rate limiting (k[cat] 392 min[-1]), (b) the physiological trypanothione concentrations may not always saturate tryparedoxin, and (c) the rate constants for the net forward reaction of Cf21 are faster than those of the tryparedoxin reaction. The functional characteristics of tryparedoxin explain the limited capacity of trypanosomatids in coping with oxidative stress and qualify the enzyme as a potential target for the design of specific trypanocidal compounds.
Authors:
D U Gommel; E Nogoceke; M Morr; M Kiess; H M Kalisz; L Flohé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  248     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-11-24     Completed Date:  1997-11-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  913-8     Citation Subset:  IM    
Affiliation:
Gesellschaft für Biotechnologische Forschung, Braunschweig, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Catalysis
Crithidia fasciculata / chemistry*
Disulfides / metabolism
Glutathione / analogs & derivatives,  metabolism
Glutathione Disulfide / metabolism
Kinetics
Mass Spectrometry
Oxidation-Reduction
Peroxidases / metabolism
Protozoan Proteins / metabolism*
Spermidine / analogs & derivatives,  metabolism
Thioredoxins / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Disulfides; 0/Protozoan Proteins; 124-20-9/Spermidine; 27025-41-8/Glutathione Disulfide; 52500-60-4/Thioredoxins; 70-18-8/Glutathione; 96304-42-6/trypanothione; EC 1.11.1.-/Peroxidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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