Structural and mechanistic studies of Trypanosoma brucei ornithine decarboxylase

2000 ◽  
pp. 327-332
Author(s):  
Margaret A. Phillips
Keyword(s):  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Mechanistic Studies

Trypanosoma brucei brucei: Regulation of ornithine decarboxylase in procyclic forms and trypomastigotes

1989 ◽  
Vol 68 (4) ◽  
pp. 392-402 ◽  
Author(s):  
Cyrus J. Bacchi ◽  
Joanne Garofalo ◽  
Angela Santana ◽  
Joseph C. Hannan ◽  
Alan J. Bitonti ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Trypanosoma Brucei Brucei

The translation initiation site of recombinant Trypanosoma brucei ornithine decarboxylase varies with different promoters

1992 ◽  
Vol 55 (1-2) ◽  
pp. 95-104 ◽  
Author(s):  
Douglas A. Kuntz ◽  
Margaret A. Phillips ◽  
Tracey D.E. Moore ◽  
Sydney P. Craig ◽  
Kathryn E. Bass ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Translation Initiation ◽  
Initiation Site ◽  
Translation Initiation Site

scholarly journals Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D,L-alpha-difluoromethylornithine.

1997 ◽  
Vol 41 (9) ◽  
pp. 1922-1925 ◽  
Author(s):  
M Iten ◽  
H Mett ◽  
A Evans ◽  
J C Enyaru ◽  
R Brun ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Turnover Rate ◽  
Drug Uptake ◽  
East African ◽  
Trypanosoma Brucei Rhodesiense ◽  
Significant Difference ◽  
Enzyme Turnover ◽  
Time Required ◽  
Substantial Degree

Ornithine decarboxylase (ODC), the target enzyme of D,L-alpha-difluoromethylornithine (DFMO), was investigated in four DFMO-tolerant Trypanosoma brucei rhodesiense isolates from East Africa and two DFMO-susceptible T. b. gambiense isolates from West Africa. Neither drug uptake nor inhibition of ODC activity by DFMO in cellular extracts differed in the two trypanosome subspecies. However, the specific ODC activity of the cellular extracts was three times as high in T. b. rhodesiense isolates as in T. b. gambiense isolates. Furthermore, a significant difference in the turnover rate of ODC was observed. The time required to induce a 50% reduction of T. b. rhodesiense ODC activity under cycloheximide pressure (tentative half-life) was about 4.3 h, whereas that required for T. b. gambiense ODC was longer than 18 h. We concluded that the higher specific ODC activity and faster enzyme turnover contributed to a substantial degree to the DFMO tolerance observed in the East African T. b. rhodesiense isolates.

scholarly journals RNA Interference-Mediated Silencing of Ornithine Decarboxylase and Spermidine Synthase Genes in Trypanosoma brucei Provides Insight into Regulation of Polyamine Biosynthesis

2009 ◽  
Vol 8 (5) ◽  
pp. 747-755 ◽  
Author(s):  
Yanjing Xiao ◽  
Diane E. McCloskey ◽  
Margaret A. Phillips
Keyword(s):  
Cell Death ◽  
Rna Interference ◽  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Cellular Response ◽  
Sleeping Sickness ◽  
Spermidine Synthase ◽  
African Sleeping Sickness ◽  
Polyamine Biosynthesis ◽  
Insight Into

ABSTRACT Polyamine biosynthesis is a drug target for the treatment of African sleeping sickness; however, mechanisms regulating the pathway in Trypanosoma brucei are not well understood. Recently, we showed that RNA interference (RNAi)-mediated gene silencing or the inhibition of S-adenosylmethionine decarboxylase (AdoMetDC) led to the upregulation of the AdoMetDC activator, prozyme, and ornithine decarboxylase (ODC) proteins. To determine if this regulatory response is specific to AdoMetDC, we studied the effects of the RNAi-induced silencing of the spermidine synthase (SpdSyn) and ODC genes in bloodstream form T. brucei. The knockdown of either gene product led to the depletion of the polyamine and trypanothione pools and to cell death. Decarboxylated AdoMet levels were elevated, while AdoMet was not affected. There was no significant effect on the protein levels of other polyamine pathway enzymes. The treatment of parasites with the ODC inhibitor α-difluoromethylornithine gave similar results to those observed for ODC knockdown. Thus, the cellular response to the loss of AdoMetDC activity is distinctive, suggesting that AdoMetDC activity controls the expression levels of the other spermidine biosynthetic enzymes. RNAi-mediated cell death occurred more rapidly for ODC than for SpdSyn. Further, the ODC RNAi cells were rescued by putrescine, but not spermidine, suggesting that the depletion of both putrescine and spermidine is more detrimental than the depletion of spermidine alone. This finding may contribute to the effectiveness of ODC as a target for the treatment of African sleeping sickness, thus providing important insight into the mechanism of action of a key antitrypanosomal agent.

Regulated degradation of ornithine decarboxylase requires interaction with the polyamine-inducible protein antizyme

1992 ◽  
Vol 12 (8) ◽  
pp. 3556-3562
Author(s):  
X Li ◽  
P Coffino
Keyword(s):  
Amino Acid ◽  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Chimeric Mouse ◽  
Protein Inhibitor ◽  
Intracellular Degradation ◽  
Inducible Protein ◽  
Equivalent Region

Intracellular degradation of vertebrate ornithine decarboxylase (ODC) is accelerated by polyamines, the products of the pathway controlled by ODC. Antizyme, a reversible, tightly binding protein inhibitor of ODC activity, is believed to be involved in this process. Mouse and Trypanosoma brucei ODCs are structurally similar, but the trypanosome enzyme, unlike that of the mouse, is not regulated by intracellular polyamines when expressed in hamster cells (L. Ghoda, D. Sidney, M. Macrae, and P. Coffino, Mol. Cell. Biol. 12:2178-2185, 1992). We found that mouse ODC interacts with antizyme in vitro but trypanosome ODC does not. To localize the region necessary for binding, we made a series of enzymatically active chimeric mouse-trypanosome ODCs and tested them for antizyme interaction. Replacing residues 117 to 140 within the 461-amino-acid mouse ODC sequence with the equivalent region of trypanosome ODC disrupted both antizyme binding and in vivo regulation. Formation of an antizyme-ODC complex is therefore required for regulated degradation.

Stabilization and immobilization of Trypanosoma brucei ornithine decarboxylase for the biobased production of 1,4-diaminobutane

2011 ◽  
Vol 13 (5) ◽  
pp. 1167 ◽  
Author(s):  
Paul M. Könst ◽  
Maurice C. R. Franssen ◽  
Elinor L. Scott ◽  
Johan P. M. Sanders
Keyword(s):  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase ◽  
Biobased Production

scholarly journals Mouse ornithine decarboxylase is stable in Trypanosoma brucei.

1992 ◽  
Vol 267 (16) ◽  
pp. 11034-11037
Author(s):  
K.E. Bass ◽  
J.M. Sommer ◽  
Q.L. Cheng ◽  
C.C. Wang
Keyword(s):  
Trypanosoma Brucei ◽  
Ornithine Decarboxylase
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