Novel organization and sequences of five genes encoding all six enzymes for de novo pyrimidine biosynthesis in Trypanosoma cruzi

Citation
Gh. Gao et al., Novel organization and sequences of five genes encoding all six enzymes for de novo pyrimidine biosynthesis in Trypanosoma cruzi, J MOL BIOL, 285(1), 1999, pp. 149-161
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
JOURNAL OF MOLECULAR BIOLOGY
ISSN journal
0022-2836 → ACNP
Volume
285
Issue
1
Year of publication
1999
Pages
149 - 161
Database
ISI
SICI code
0022-2836(19990108)285:1<149:NOASOF>2.0.ZU;2-D
Abstract
A 25 kb segment of genomic DNA from Trypanosoma cruzi, the causative agent of Chagas' disease, was sequenced. It contains five genes, pyr1, Pyr2, Pyr3 , pyr4, and pyr6-5, encoding all six enzymes involved in de novo pyrimidine biosynthesis, glutamine-dependent carbamoyl-phosphate synthetase, aspartat e carbamoyltransferase, dihydroorotase, dihydroorotate dehydrogenase, and o rotidine-5'-phosphate decarboxylase Linked with oro tate phosphoribosyltran sferase, respectively. The pyr genes constitute a polycistronic transcripti on unit on an 800 kb chromosomal DNA in the order of pyr1, pyr3, pyr6-5, py r2, and pyr4 from the 5' terminus, with intervening sequences of 2.2, 0.4, 8.1, and 0.8 kb. The amino acid sequences deduced from the trypanosomatid p yr genes, except for pyr6, showed closer similarities to mammalian and yeas t sequences, and less similarity to archaeal and bacterial sequences. The l ast two enzymes encoded by a single gene, pyr6-5, are covalently linked in the order opposite to mammalian pyr5-6, and possess a putative glycosomal t argeting signal tripeptide, serine-lysine-leucine, at the C terminus. The c alculated isoelectric points of 9.3 and 9.9 are also diagnostic of the glyc osomal localization of these enzymes. We conclude that the T. cruzi pyr gen e organization represents an early progenitor in de novo pyrimidine biosynt hesis in eukaryotic lineage, and that the independent pyr genes may have ev olved before the gene fusion events that resulted in the three mammalian-ty pe genes, pyr1-3-2, pyr4, and pyr5-6, for UMP synthesis. Peculiarities in t he trypanosomatid pyr6-5 gene product are discussed. (C) 1999 Academic Pres s.