% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Riccardi:834628,
author = {Riccardi, Laura and Arencibia, Jose M. and Bono, Luca and
Armirotti, Andrea and Girotto, Stefania and De Vivo, Marco},
title = {{L}id domain plasticity and lipid flexibility modulate
enzyme specificity in human monoacylglycerol lipase},
journal = {Biochimica et biophysica acta / Molecular and cell biology
of lipids},
volume = {1862},
number = {5},
issn = {1388-1981},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {FZJ-2017-04536},
pages = {441 - 451},
year = {2017},
abstract = {Human monoacylglycerol lipase (MAGL) is a
membrane-interacting enzyme that generates pro-inflammatory
signaling molecules. For this reason, MAGL inhibition is a
promising strategy to treat pain, cancer, and
neuroinflammatory diseases. MAGL can hydrolyze
monoacylglycerols bearing an acyl chain of different lengths
and degrees of unsaturation, cleaving primarily the
endocannabinoid 2-arachidonoylglycerol. Importantly, the
enzymatic binding site of MAGL is confined by a
75-amino-acid-long, flexible cap domain, named ‘lid
domain’, which is structurally similar to that found in
several other lipases. However, it is unclear how lid domain
plasticity affects catalysis in MAGL. By integrating
extensive molecular dynamics simulations and free-energy
calculations with mutagenesis and kinetic experiments, we
here define a lid-domain-mediated mechanism for substrate
selection and binding in MAGL catalysis. In particular, we
clarify the key role of Phe159 and Ile179, two conserved
residues within the lid domain, in regulating substrate
specificity in MAGL. We conclude by proposing that other
structurally related lipases may share this
lid-domain-mediated mechanism for substrate specificity.},
cin = {IAS-5 / INM-9},
ddc = {570},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000400715800001},
pubmed = {pmid:28088576},
doi = {10.1016/j.bbalip.2017.01.002},
url = {https://juser.fz-juelich.de/record/834628},
}