Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling.
نویسندگان
چکیده
Modelling of the mechanism of covalent adduct formation by the inhibitor O-arylcarbamate URB524 in FAAH shows that only one of the two possible inhibitor binding orientations is consistent with the experimentally observed irreversible carbamoylation of the nucleophile serine: this is a potentially crucial insight for designing new covalent inhibitors of this promising drug target.
منابع مشابه
Insights into the mechanism and inhibition of fatty acid amide hydrolase from quantum mechanics/molecular mechanics (QM/MM) modelling.
FAAH (fatty acid amide hydrolase) is a promising target for the treatment of several central nervous system and peripheral disorders. Combined QM/MM (quantum mechanics/molecular mechanics) calculations have elucidated the role of its unusual catalytic triad in the hydrolysis of oleamide and oleoylmethyl ester substrates, and have identified the productive inhibitor-binding orientation for the c...
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عنوان ژورنال:
- Chemical communications
دوره 2 شماره
صفحات -
تاریخ انتشار 2008