The Search for Covalently Ligandable Proteins in Biological Systems.
This commentary highlights the recent article published in Nature, June 2016, titled: "Proteome-wide covalent ligand discovery in native biological systems". They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here.
Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan. shahbiochemist@gmail.com.|Department of Biochemistry, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa 25120, Pakistan. shahbiochemist@gmail.com.
Syed Lal
SL
Badshah
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. yahia@ksu.edu.sa.
Yahia Nasser
YN
Mabkhot
D002460:Cell Line; D003545:Cysteine / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D020543:Proteome / Q000032:analysis / Q000737:chemistry*
D008024:Ligands; D020543:Proteome; D003545:Cysteine
covalent binding ligands; druggable cysteines; fragment-based ligand discovery; isotopic tandem orthogonal proteolysis‒activity-based protein profiling; methyl transferase; protease caspase enzyme