Abstract
QM/MM modelling of FAAH inactivation by O-biphenyl-3-yl carbamates identifies the deprotonation of Ser241 as the key reaction step, explaining why FAAH is insensitive to the electron-donor effect of conjugated substituents; this may aid design of new inhibitors with improved selectivity and in vivo potency.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amidohydrolases / antagonists & inhibitors*
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Amidohydrolases / metabolism
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Binding Sites
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology
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Carbamates / chemistry*
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Carbamates / pharmacology
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Computer Simulation
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Protons
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Quantum Theory
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Structure-Activity Relationship
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Thermodynamics
Substances
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Biphenyl Compounds
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Carbamates
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Enzyme Inhibitors
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Protons
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cyclohexylcarbamic acid biphenyl-3-yl ester
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Amidohydrolases
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fatty-acid amide hydrolase