5I2F

Human Histidine Triad Nucleotide Binding Protein 1 (hHint1) with bound sulfamide inhibitor Bio-AMS

Summary for 5I2F

• Entry DOI: 10.2210/pdb5i2f/pdb
• Related: 3TW2 4EQE 4EQG 4EQH 5I2E
• Descriptor: Histidine triad nucleotide-binding protein 1, 1,2-ETHANEDIOL, 5'-deoxy-5'-[({5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl}sulfamoyl)amino]adenosine, ... (4 entities in total)
• Functional Keywords: hint, histidine triad, hit, hydrolase inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P49773
• Total number of polymer chains: 2
• Total formula weight: 28888.14

Authors

Maize, K.M.,Finzel, B.C. (deposition date: 2016-02-08, release date: 2016-06-22, Last modification date: 2023-09-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.25 Å)