Hydrogen bonding in human p450-substrate interactions: a major contribution to binding affinity.
The importance of hydrogen bonding, a relatively strong intermolecular force of attraction between molecules in biological systems, is discussed in the respect of P450 substrate affinity towards one or more of the human P450 enzymes that are generally associated with drug and other xenobiotic metabolism. It is shown that calculation of hydrogen bond distances and energies based on simple empirical relationships provide values that agree closely with experimental findings. It is thus possible to estimate the hydrogen bond contribution to P450 enzyme-substrate binding affinity based on modelled interactions and by use of these relatively simple formulae, particularly when employed in conjunction with substrate-lipophilicity relationships.
Lewis
David F V
DF
School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK. d.lewis@surrey.ac.uk
D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry; D001665:Binding Sites; D003374:Coumarins / Q000737:chemistry; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D006860:Hydrogen Bonding; D006899:Mixed Function Oxygenases / Q000737:chemistry; D011485:Protein Binding
D003374:Coumarins; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6