6UEK

Structure of Urocanate Hydratase from Trypanosoma cruzi in complex with NAD+

6UEK の概要

• エントリーDOI: 10.2210/pdb6uek/pdb
• 分子名称: Urocanate hydratase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: chagas disease, urocanate hydratase, nad+, interdomain movement, lyase
• 由来する生物種: Trypanosoma cruzi
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 305402.01

構造登録者

Boreiko, S.,Silva, M.,Melo, R.F.P.,Silber, A.M.,Iulek, J. (登録日: 2019-09-21, 公開日: 2020-01-15, 最終更新日: 2023-10-11)

主引用文献

Boreiko, S.,Silva, M.,de F P Melo, R.,Silber, A.M.,Iulek, J.
Structure of Urocanate Hydratase from the protozoan Trypanosoma cruzi.
Int.J.Biol.Macromol., 146:716-724, 2019

PubMed Abstract: The enzyme Urocanate Hydratase (UH) participates in the catabolic pathway of L-histidine. Trypanosoma cruzi Urocanate Hydratase (TcUH) is identified as a therapeutic molecular target in the WHO/TDR Targets Database. We report the 3D structure determination and number of features of TcUH, and compared it to other few available bacterial UH structures. Each monomer presents two domains and one NAD molecule. Superpositions revealed differences in the relative orientation of domains within monomers, such that TcUH monomer A resembles Urocanate Hydratase from Geobacillus kaustophilus (GkUH) (open conformation), while monomer C resembles Urocanate Hydratase from Pseudomonas putida (PpUH) and Urocanate Hydratase from Bacillus subtilis (BsUH) (closed conformations). We use the structure of TcUH to make considerations about 3 non-deleterious and 2 deleterious mutations found in human UHs: non-deleterious mutations could be accommodated without large displacements or interaction interruptions, whereas deleterious mutations in one case might disrupt an α-helix (as previously suggested) and in the other case, besides disrupting the enzyme interaction with the substrate, might interfere with interdomain movement.

PubMed: 31843618
DOI: 10.1016/j.ijbiomac.2019.12.101

実験手法

X-RAY DIFFRACTION (2.16 Å)