Issue 2, 2008
From the journal:

Chemical Communications

Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling†

Alessio Lodola,a   Marco Mor,a   Silvia Rivara,a   Christo Christov,b   Giorgio Tarzia,c   Daniele Piomellid  and  Adrian J. Mulholland*b  

* Corresponding authors

a Dipartimento Farmaceutico, Università degli Studi di Parma, Parma, Italy
E-mail: alessio.lodola@unipr.it

b School of Chemistry, University of Bristol, Bristol, UK
E-mail: Adrian.Mulholland@bristol.ac.uk

c Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Urbino “Carlo Bo”, Urbino, Italy

d Department of Pharmacology, University of California, Irvine, California, USA

Abstract

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.

Graphical abstract: Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling

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DOI
https://doi.org/10.1039/B714136J
Article type
Communication
Submitted
13 Sep 2007
Accepted
12 Oct 2007
First published
19 Oct 2007

Chem. Commun., 2008, 214-216

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Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling

A. Lodola, M. Mor, S. Rivara, C. Christov, G. Tarzia, D. Piomelli and A. J. Mulholland, Chem. Commun., 2008, 214 DOI: 10.1039/B714136J

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