5I2E

Human Histidine Triad Nucleotide Binding Protein 1 (Hint1) with Bound Sulfamate Inhibitor 3a:3-(5-O-{[3-(1H-indol-3-yl)propanoyl]sulfamoyl}-beta-D-ribofuranosyl)-3H-imidazo[2,1-i]purine

5I2E の概要

• エントリーDOI: 10.2210/pdb5i2e/pdb
• 関連するPDBエントリー: 3TW2 4EQE 4EQG 4EQH 5I2F
• 分子名称: Histidine triad nucleotide-binding protein 1, 3-(5-O-{[3-(1H-indol-3-yl)propanoyl]sulfamoyl}-beta-D-ribofuranosyl)-3H-imidazo[2,1-i]purine, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: hint, histidine triad, hit, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P49773
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28826.01

構造登録者

Strom, A.M.,Finzel, B.C.,Wagner, C.R. (登録日: 2016-02-08, 公開日: 2016-06-22, 最終更新日: 2023-09-27)

主引用文献

Shah, R.,Strom, A.,Zhou, A.,Maize, K.M.,Finzel, B.C.,Wagner, C.R.
Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1.
Acs Med.Chem.Lett., 7:780-784, 2016

PubMed Abstract: Hint1 has recently emerged to be an important target of interest due to its involvement in the regulation of a broad range of CNS functions including opioid signaling, tolerance, neuropathic pain, and nicotine dependence. A series of inhibitors were rationally designed, synthesized, and tested for their inhibitory activity against hHint1 using isothermal titration calorimetry (ITC). The studies resulted in the development of the first small-molecule inhibitors of hHint1 with submicromolar binding affinities. A combination of thermodynamic and high-resolution X-ray crystallographic studies provides an insight into the biomolecular recognition of ligands by hHint1. These novel inhibitors have potential utility as molecular probes to better understand the role and function of hHint1 in the CNS.

PubMed: 27563403
DOI: 10.1021/acsmedchemlett.6b00169

実験手法

X-RAY DIFFRACTION (1.6 Å)