RT Journal Article
T1 Exploring the Water-Binding Pocket of the Type II Dehydroquinase Enzyme in the Structure-Based Design of Inhibitors
A1 Blanco Rodríguez, Beatriz
A1 Sedes, Antía
A1 Peón López, Antonio
A1 Otero Casas, José Manuel
A1 Raaij, Mark J. van
A1 Thompson, Paul
A1 Hawkins, Alastair R.
A1 González Bello, Concepción
AB Structural and computational studies to explore the WAT1 binding pocket in the structure-based design of inhibitors against the type II dehydroquinase (DHQ2) enzyme are reported. The crystal structures of DHQ2 from M. tuberculosis in complex with four of the reported compounds are described. The electrostatic interaction observed between the guanidinium group of the essential arginine and the carboxylate group of one of the inhibitors in the reported crystal structures supports the recently suggested role of this arginine as the residue that triggers the release of the product from the active site. The results of the structural and molecular dynamics simulation studies revealed that the inhibitory potency is favored by promoting interactions with WAT1 and the residues located within this pocket and, more importantly, by avoiding situations where the ligands occupy the WAT1 binding pocket. The new insights can be used to advantage in the structure-based design of inhibitors
PB American Chemical Society
SN 0022-2623
YR 2014
FD 2014
LK http://hdl.handle.net/10347/16932
UL http://hdl.handle.net/10347/16932
LA eng
NO Blanco, B., Sedes, A., Peón, A., Otero, J., van Raaij, M., & Thompson, P. et al. (2014). Exploring the Water-Binding Pocket of the Type II Dehydroquinase Enzyme in the Structure-Based Design of Inhibitors. Journal Of Medicinal Chemistry, 57(8), 3494-3510. doi: 10.1021/jm500175z
NO Financial support from the Spanish Ministry of Science and Innovation (Grant SAF2010-15076) and the Xunta de Galicia (Grant GRC2013/041) is gratefully acknowledged. B.B. and A.P. thank the Spanish Ministry of Education for their respective FPU fellowships. A.S. thanks the Spanish Ministry of Economy andCompetitiveness for her FPI fellowship. J.M.O. thanks the Xunta de Galicia for a Plan I2C postdoctoral fellowship
DS Minerva
RD 29 abr 2026