Studies on ligand binding to histidine triad nucleotide binding protein 1.
Histidine triad nucleotide binding protein (HINT1) is an intracellular protein that binds purine mononucleotides. Strong sequence conservation suggests that these proteins play a fundamental role in cell biology, however its exact cellular function continues to remain elusive. nuclear magnetic resonance (NMR) studies using STD and HSQC were conducted to observe ligand binding to HINT1. These studies were confirmed using fluorescence spectroscopy titrations. We found that AICAR, the first non-phosphate containing ligand, binds to mouse histidine triad nucleotide binding protein 1 (HINT1). Chemical shift perturbations are mapped onto the X-ray structure showing AICAR binds at the same site as GMP. The NMR results demonstrated that this method will be valuable for the future screening of small molecules that can be used to modulate the function of HINT1.
Bai
Guoyun
G
University of Maryland, Department of Pharmaceutical Sciences, Baltimore, MD 21201, United States.
Feng
Bo
B
Wang
Jia Bei
JB
Pozharski
Edwin
E
Shapiro
Michael
M
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D018360:Crystallography, X-Ray; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012263:Ribonucleosides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
C489275:Hint1 protein, mouse; D008024:Ligands; D009419:Nerve Tissue Proteins; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine