Molecular docking of thiamine reveals similarity in binding properties between the prion protein and other thiamine-binding proteins

Journal of Molecular Modeling
Nataraj S PagadalaDavid S Wishart


Prion-induced diseases are a global health concern. The lack of effective therapy and 100% mortality rates for such diseases have made the prion protein an important target for drug discovery. Previous NMR experimental work revealed that thiamine and its derivatives bind the prion protein in a pocket near the N-terminal loop of helix 1, and conserved intermolecular interactions were noted between thiamine and other thiamine-binding proteins. Furthermore, water-mediated interactions were observed in all of the X-ray crystallographic structures of thiamine-binding proteins, but were not observed in the thiamine-prion NMR study. To better understand the potential role of water in thiamine-prion binding, a docking study was employed using structural X-ray solvent. Before energy minimization, docked thiamine assumed a "V" shape similar to some of the known thiamine-dependent proteins. Following minimization with NMR-derived restraints, the "F" conformation was observed. Our findings confirmed that water is involved in ligand stabilization and phosphate group interaction. The resulting refined structure of thiamine bound to the prion protein allowed the 4-aminopyrimidine ring of thiamine to π-stack with Tyr150, and facilitated hydrog...Continue Reading


Mar 27, 1979·Biochimica Et Biophysica Acta·A Iwashima, H Nishimura
May 31, 1972·Journal of the American Chemical Society·J Pletcher, M Sax
Jan 3, 1997·Science·D KernG Hübner
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S B Prusiner
Jun 23, 2001·Journal of Molecular Biology·D E TimmR A Harris
Jul 4, 2001·Structure·L J BakerD E Timm
Jul 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kazuo KuwataShigeru Katamine
Nov 21, 2008·Acta Crystallographica. Section D, Biological Crystallography·Katherine H SippelRobert McKenna
Aug 19, 2011·The FEBS Journal·Rolando Perez-PineiroDavid S Wishart


Jan 26, 2017·Expert Opinion on Drug Discovery·Nataraj S PagadalaRakesh Bhat
Sep 17, 2019·Biochemistry. Biokhimii︠a︡·V A AleshinV I Bunik

Related Concepts

Thiamine-binding protein
Carrier Proteins
Hydrogen Bonding
Plasma Protein Binding Capacity
Protein Conformation
Thiamine Mononitrate
Protein Conformation, beta-Strand

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.


Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.