Systematic discovery of molecular probes targeting multiple non-orthosteric and spatially distinct sites in the botulinum neurotoxin subtype A (BoNT/A)

Molecular and Cellular Probes
Saedeh Dadgar, Wely B Floriano

Abstract

The development of molecular probes targeting proteins has traditionally relied on labeling compounds already known to bind to the protein of interest. These known ligands bind to orthosteric or allosteric sites in their target protein as a way to control their activity. Binding pockets other than known orthosteric or allosteric sites may exist that are large enough to accommodate a ligand without significantly disrupting protein activity. Such sites may provide opportunities to discriminate between subtypes or other closely related proteins, since they are under less evolutionary pressure to be conserved. The Protein Scanning with Virtual Ligand Screening (PSVLS) approach was previously used to identify a novel inhibitor and a fluorescent probe against the catalytic site of the botulinum neurotoxin subtype A (BoNT/A). PSVLS screens compound databases against multiple sites within a target protein, and the results for all the sites probed against BoNT/A, not only the catalytic site, are available online. Here, we analyze the PSVLS data for multiple sites in order to identify molecular probes with affinity for binding pockets other than the catalytic site of BoNT/A. BoNT/A is a large protein with a light (LC) and a heavy (HC) ch...Continue Reading

References

Jun 4, 1998·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·J SattaT Juvonen
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·D FasshauerR Jahn
Jul 18, 2002·Nature Reviews. Drug Discovery·Arthur Christopoulos
Dec 6, 2003·Pharmacological Reviews·Richard R NeubigUNKNOWN International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification
Dec 30, 2003·Journal of Medicinal Chemistry·Wely B FlorianoWilliam A Goddard
Sep 27, 2005·Molecular Pharmacology·Jürgen Wess
Nov 23, 2006·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A B WardA Berardelli
Nov 23, 2006·The Protein Journal·Shuowei CaiBal Ram Singh
Apr 5, 2011·Phytochemistry·Mark A Taylor, Paul D Fraser
May 1, 2010·Toxins·Frank J LebedaMichael Adler
Nov 18, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Neil A DevenportColin S Creaser
Mar 1, 2012·Thorax·John D MaclayWilliam Macnee
May 1, 2012·Bioorganic & Medicinal Chemistry Letters·Garry R SmithTobin J Dickerson
Feb 19, 2013·Bioorganic & Medicinal Chemistry Letters·Naoki TomitaAtsuo Baba
Mar 1, 2013·Journal of Medicinal Chemistry·Feng LiuJian Jin
Sep 12, 2013·Molecular Pharmacology·J Robert LaneVsevolod Katritch

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