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5i2e

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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

Structural highlights

5i2e is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HINT1_HUMAN Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity).

Publication Abstract from PubMed

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.

Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1.,Shah R, Strom A, Zhou A, Maize KM, Finzel BC, Wagner CR ACS Med Chem Lett. 2016 Jun 15;7(8):780-4. doi: 10.1021/acsmedchemlett.6b00169., eCollection 2016 Aug 11. PMID:27563403^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shah R, Strom A, Zhou A, Maize KM, Finzel BC, Wagner CR. Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1. ACS Med Chem Lett. 2016 Jun 15;7(8):780-4. doi: 10.1021/acsmedchemlett.6b00169., eCollection 2016 Aug 11. PMID:27563403 doi:http://dx.doi.org/10.1021/acsmedchemlett.6b00169