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

Alessio Lodola; Marco Mor; Silvia Rivara; Christo Christov; Giorgio Tarzia; Daniele Piomelli; Adrian Mulholland

doi:10.1039/b714136j

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

Alessio Lodola, Marco Mor, Silvia Rivara, Christo Christov, Giorgio Tarzia, Daniele Piomelli, Adrian Mulholland

Research output: Contribution to journal › Article › peer-review

67 Citations (Scopus)

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.

Original language	English
Pages (from-to)	214-216
Journal	Chemical Communications
Volume	2008
Issue number	2
DOIs	https://doi.org/10.1039/b714136j
Publication status	Published - 2008

Keywords

Fatty acids
Inhibitors
Chemical

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10.1039/b714136j

Cite this

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

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.",

keywords = "Fatty acids, Inhibitors, Chemical",

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pages = "214--216",

journal = "Chemical Communications",

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T1 - Identification of productive inhibitor binding orientation in fatty acid amide hydrolase (FAAH) by QM/MM mechanistic modelling

AU - Lodola, Alessio

AU - Mor, Marco

AU - Rivara, Silvia

AU - Christov, Christo

AU - Tarzia, Giorgio

AU - Piomelli, Daniele

AU - Mulholland, Adrian

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Fatty acids

KW - Inhibitors

KW - Chemical

UR - https://www.scopus.com/pages/publications/37349122437

U2 - 10.1039/b714136j

DO - 10.1039/b714136j

M3 - Article

SN - 0022-4936

SN - 1359-7345

SN - 1364-548X

VL - 2008

SP - 214

EP - 216

JO - Chemical Communications

JF - Chemical Communications

IS - 2

ER -

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

Abstract

Keywords

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