A Unique Dual Activity Amino Acid Hydroxylase in Toxoplasma gondii

被引:207
作者
Gaskell, Elizabeth A.
Smith, Judith E.
Pinney, John W.
Westhead, Dave R.
McConkey, Glenn A.
机构
[1] Institute of Integrative and Comparative Biology, University of Leeds, Leeds
[2] Institute of Molecular and Cellular Biology, University of Leeds, Leeds
[3] Faculty of Life Sciences, University of Manchester, Manchester
来源
PLOS ONE | 2009年 / 4卷 / 03期
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
D O I
10.1371/journal.pone.0004801
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The genome of the protozoan parasite Toxoplasma gondii was found to contain two genes encoding tyrosine hydroxylase; that produces L-DOPA. The encoded enzymes metabolize phenylalanine as well as tyrosine with substrate preference for tyrosine. Thus the enzymes catabolize phenylalanine to tyrosine and tyrosine to L-DOPA. The catalytic domain descriptive of this class of enzymes is conserved with the parasite enzyme and exhibits similar kinetic properties to metazoan tyrosine hydroxylases, but contains a unique N-terminal extension with a signal sequence motif. One of the genes, TgAaaH1, is constitutively expressed while the other gene, TgAaaH2, is induced during formation of the bradyzoites of the cyst stages of the life cycle. This is the first description of an aromatic amino acid hydroxylase in an apicomplexan parasite. Extensive searching of apicomplexan genome sequences revealed an ortholog in Neospora caninum but not in Eimeria, Cryptosporidium, Theileria, or Plasmodium. Possible role(s) of these bi-functional enzymes during host infection are discussed.
引用
收藏
页数:10
相关论文
共 43 条
[1]   Toxoplasma gondii: The growth characteristics of three virulent strains [J].
Appleford, PJ ;
Smith, JE .
ACTA TROPICA, 1997, 65 (02) :97-104
[2]   Improved prediction of signal peptides: SignalP 3.0 [J].
Bendtsen, JD ;
Nielsen, H ;
von Heijne, G ;
Brunak, S .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 340 (04) :783-795
[3]   GeneWise and genomewise [J].
Birney, E ;
Clamp, M ;
Durbin, R .
GENOME RESEARCH, 2004, 14 (05) :988-995
[4]   Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells [J].
Blader, IJ ;
Manger, ID ;
Boothroyd, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (26) :24223-24231
[5]   Targeted disruption of the bradyzoite-specific gene BAG1 does not prevent tissue cyst formation in Toxoplasma gondii [J].
Bohne, W ;
Hunter, CA ;
White, MW ;
Ferguson, DJP ;
Gross, U ;
Roos, DS .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1998, 92 (02) :291-301
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]   Enzyme-specific profiles for genome annotation: PRIAM [J].
Claudel-Renard, C ;
Chevalet, C ;
Faraut, T ;
Kahn, D .
NUCLEIC ACIDS RESEARCH, 2003, 31 (22) :6633-6639
[8]   COMPARISON OF ISOENZYME PROFILES OF TOXOPLASMA-GONDII TACHYZOITES PRODUCED UNDER DIFFERENT CULTURE CONDITIONS [J].
DARDE, ML ;
BOUTEILLE, B ;
PESTREALEXANDRE, M .
PARASITOLOGY RESEARCH, 1990, 76 (04) :367-371
[9]   Characterization of chimeric pterin-dependent hydroxylases: Contributions of the regulatory domains of tyrosine and phenylalanine hydroxylase to substrate specificity [J].
Daubner, SC ;
Hillas, PJ ;
Fitzpatrick, PF .
BIOCHEMISTRY, 1997, 36 (39) :11574-11582
[10]   Reversing the substrate specificities of phenylalanine and tyrosine hydroxylase: Aspartate 425 of tyrosine hydroxylase is essential for L-DOPA formation [J].
Daubner, SC ;
Melendez, J ;
Fitzpatrick, PF .
BIOCHEMISTRY, 2000, 39 (32) :9652-9661