Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors.
The significance of halogen bonding in protein-ligand interactions has been recognized recently. We present here the first comprehensive thermodynamic and structural characterization of halogen bonding in PDE5-inhibitor interactions. ITC studies reveal that binding strength of the halogen bonding between chlorine, bromine, and iodine of inhibitor and the protein is -1.57, -3.09, and -5.59 kJ/mol, respectively. The halogens interact with the designed residue Y612 and an unexpected buried water molecule.
CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS) , 555 Zuchongzhi Road, Shanghai 201203, China.
Jing
J
Ren
Yang
Y
He
Wuyan
W
Chen
Tiantian
T
Chen
Guan
G
Wang
Zhen
Z
Wang
Zhijian
Z
Xu
Xiaomin
X
Luo
Weiliang
W
Zhu
Hualiang
H
Jiang
Jingshan
J
Shen
Yechun
Y
Xu
D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000737:chemistry*; D006219:Halogens / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry*; D013816:Thermodynamics
D006219:Halogens; D008024:Ligands; D058986:Phosphodiesterase 5 Inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5