5N29

An improved model of the Trypanosoma brucei CTP synthase glutaminase domain:acivicin complex.

5N29 の概要

• エントリーDOI: 10.2210/pdb5n29/pdb
• 分子名称: CTP synthase, CHLORIDE ION (3 entities in total)
• 機能のキーワード: ctp synthase, ligase
• 由来する生物種: Trypanosoma brucei gambiense (strain MHOM/CI/86/DAL972)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30868.52

構造登録者

de Souza, J.,Dawson, A.,Hunter, W. (登録日: 2017-02-07, 公開日: 2017-04-05, 最終更新日: 2025-04-09)

主引用文献

Oliveira de Souza, J.,Dawson, A.,Hunter, W.N.
An Improved Model of the Trypanosoma brucei CTP Synthetase Glutaminase Domain-Acivicin Complex.
ChemMedChem, 12:577-579, 2017

PubMed Abstract: The natural product acivicin inhibits the glutaminase activity of cytidine triphosphate (CTP) synthetase and is a potent lead compound for drug discovery in the area of neglected tropical diseases, specifically trypanosomaisis. A 2.1-Å-resolution crystal structure of the acivicin adduct with the glutaminase domain from Trypanosoma brucei CTP synthetase has been deposited in the RCSB Protein Data Bank (PDB) and provides a template for structure-based approaches to design new inhibitors. However, our assessment of that data identified deficiencies in the model. We now report an improved and corrected inhibitor structure with changes to the chirality at one position, the orientation and covalent structure of the isoxazoline moiety, and the location of a chloride ion in an oxyanion binding site that is exploited during catalysis. The model is now in agreement with established chemical principles and allows an accurate description of molecular recognition of the ligand and the mode of binding in a potentially valuable drug target.

PubMed: 28333400
DOI: 10.1002/cmdc.201700118

実験手法

X-RAY DIFFRACTION (2.1 Å)