4TXM

Crystal structure of uridine phosphorylase from Schistosoma mansoni in complex with thymine

4TXM の概要

• エントリーDOI: 10.2210/pdb4txm/pdb
• 関連するPDBエントリー: 4TXH 4TXJ 4TXL 4TXN
• 分子名称: Uridine phosphorylase, SULFATE ION, THYMINE, ... (4 entities in total)
• 機能のキーワード: uridine phosphorylase, transferase
• 由来する生物種: Schistosoma mansoni (Blood fluke)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65743.55

構造登録者

Marinho, A.,Torini, J.,Romanello, L.,Cassago, A.,DeMarco, R.,Brandao-Neto, J.,Pereira, H.M. (登録日: 2014-07-03, 公開日: 2015-10-14, 最終更新日: 2023-09-27)

主引用文献

da Silva Neto, A.M.,Torini de Souza, J.R.,Romanello, L.,Cassago, A.,Serrao, V.H.,DeMarco, R.,Brandao-Neto, J.,Garratt, R.C.,Pereira, H.D.
Analysis of two Schistosoma mansoni uridine phosphorylases isoforms suggests the emergence of a protein with a non-canonical function.
Biochimie, 125:12-22, 2016

PubMed Abstract: Reports of Schistosoma mansoni strains resistant to praziquantel, the only therapeutic strategy available for the treatment of schistosomiasis, have motivated the scientific community towards the search for new possible therapies. Biochemical characterization of the parasite's metabolism is an essential component for the rational development of new therapeutic alternatives. One of the so far uncharacterized enzymes is uridine phosphorylase (UP) (EC 2.4.2.3), for which the parasite genome presents two isoforms (SmUPa and SmUPb) that share 92% sequence identity. In this paper, we present crystal structures for SmUPa and SmUPb in their free states as well as bound to different ligands. This we have complemented by enzyme kinetic characterization and phylogenetic analyses. Both enzymes present an overall fold and active site structure similar to other known UPs. The kinetic analyses showed conclusively that SmUPa is a regular uridine phosphorylase but by contrast SmUPb presented no detectable activity. This is particularly noteworthy given the high level of sequence identity between the two isoforms and is probably the result of the significant differences observed for SmUPb in the vicinity of the active site itself, suggesting that it is not a UP at all. On the other hand, it was not possible to identify an alternative function for SmUPb, although our phylogenetic analyses and expression data suggest that SmUPb is still functional and plays a role in parasite metabolism. The unusual UPb isoform may open up new opportunities for understanding unique features of S. mansoni metabolism.

PubMed: 26898674
DOI: 10.1016/j.biochi.2016.02.007

実験手法

X-RAY DIFFRACTION (1.93 Å)