5EUC

The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase

5EUC の概要

• エントリーDOI: 10.2210/pdb5euc/pdb
• 分子名称: Hypoxanthine-guanine phosphoribosyltransferase (2 entities in total)
• 機能のキーワード: hprt, phosphoribosyltransferase, t. cruzi, quaternary structure, enzymatic activity modulation, stability, proteolysis, reversible oligomerization, disorder c-terminal region, bisphosphonates, transferase
• 由来する生物種: Trypanosoma cruzi (strain CL Brener)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 106666.24

構造登録者

Valsecchi, W.M.,Cousido-Siah, A.,Mitschler, A.,Podjarny, A.,Delfino, J.M.,Santos, J. (登録日: 2015-11-18, 公開日: 2016-03-30, 最終更新日: 2023-09-27)

主引用文献

Valsecchi, W.M.,Cousido-Siah, A.,Defelipe, L.A.,Mitschler, A.,Podjarny, A.,Santos, J.,Delfino, J.M.
The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase.
Biochim.Biophys.Acta, 1864:655-666, 2016

PubMed Abstract: Hypoxanthine phosphoribosyl transferase from Trypanosoma cruzi (TcHPRT) is a critical enzyme for the survival of the parasite. This work demonstrates that the full-length form in solution adopts a stable and enzymatically active tetrameric form, exhibiting large inter-subunit surfaces. Although this protein irreversibly aggregates during unfolding, oligomerization is reversible and can be modulated by low concentrations of urea. When the C-terminal region, which is predicted as a disordered stretch, is excised by proteolysis, TcHPRT adopts a dimeric state, suggesting that the C-terminal region acts as a main guide for the quaternary arrangement. These results are in agreement with X-ray crystallographic data presented in this work. On the other hand, the C-terminal region exhibits a modulatory role on the enzyme, as attested by the enhanced activity observed for the dimeric form. Bisphosphonates act as substrate-mimetics, uncovering long-range communications among the active sites. All in all, this work contributes to establish new ways applicable to the design of novel inhibitors that could eventually result in new drugs against parasitic diseases.

PubMed: 26969784
DOI: 10.1016/j.bbapap.2016.03.005

実験手法

X-RAY DIFFRACTION (2.65 Å)