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@ARTICLE{Rengachari:141360,
author = {Rengachari, S. and Bezerra, G. A. and Riegler-Berket, L.
and Gruber, C. C. and Sturm, C. and Taschler, U. and
Boeszoermenyi, A. and Dreveny, I. and Zimmermann, R. and
Gruber, K. and Oberer, M. and DESY},
title = {{T}he structure of monoacylglycerol lipase from {B}acillus
sp. {H}257 reveals unexpected conservation of the cap
architecture between bacterial and human enzymes},
journal = {Biochimica et biophysica acta / Biomembranes},
volume = {1821},
issn = {0005-2736},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {PHPPUBDB-25482},
pages = {1012-1021},
year = {2012},
note = {(c) Elsevier B.V. Code P.},
abstract = {Monoacylglycerol lipases (MGLs) catalyse the hydrolysis of
monoacylglycerol into free fatty acid and glycerol. MGLs
have been identified throughout all genera of life and have
adopted different substrate specificities depending on their
physiological role. In humans, MGL plays an integral part in
lipid metabolism affecting energy homeostasis, signalling
processes and cancer cell progression. In bacteria, MGLs
degrade short-chain monoacylglycerols which are otherwise
toxic to the organism. We report the crystal structures of
MGL from the bacterium Bacillus sp. H257 (bMGL) in its free
form at 1.2Å and in complex with phenylmethylsulfonyl
fluoride at 1.8Å resolution. In both structures, bMGL
adopts an α/β hydrolase fold with a cap in an open
conformation. Access to the active site residues, which were
unambiguously identified from the protein structure, is
facilitated by two different channels. The larger channel
constitutes the highly hydrophobic substrate binding pocket
with enough room to accommodate monoacylglycerol. The other
channel is rather small and resembles the proposed glycerol
exit hole in human MGL. Molecular dynamics simulation of
bMGL yielded open and closed states of the entrance channel
and the glycerol exit hole. Despite differences in the
number of residues, secondary structure elements, and low
sequence identity in the cap region, this first structure of
a bacterial MGL reveals striking structural conservation of
the overall cap architecture in comparison with human MGL.
Thus it provides insight into the structural conservation of
the cap amongst MGLs throughout evolution and provides a
framework for rationalising substrate specificities in each
organism.},
keywords = {Amino Acid Sequence / Bacillus: enzymology / Bacillus:
genetics / Bacterial Proteins: chemistry / Bacterial
Proteins: genetics / Bacterial Proteins: metabolism /
Catalytic Domain / Cloning, Molecular / Conserved Sequence /
Crystallography, X-Ray / Escherichia coli / Humans /
Hydrophobic and Hydrophilic Interactions / Molecular
Dynamics Simulation / Molecular Sequence Data /
Monoacylglycerol Lipases: chemistry / Monoacylglycerol
Lipases: genetics / Monoacylglycerol Lipases: metabolism /
Monoglycerides: chemistry / Monoglycerides: metabolism /
Phenylmethylsulfonyl Fluoride: chemistry / Protein
Structure, Secondary / Recombinant Proteins: chemistry /
Recombinant Proteins: genetics / Recombinant Proteins:
metabolism / Sequence Alignment / Structural Homology,
Protein / Substrate Specificity / Bacterial Proteins (NLM
Chemicals) / Monoglycerides (NLM Chemicals) / Recombinant
Proteins (NLM Chemicals) / Phenylmethylsulfonyl Fluoride
(NLM Chemicals) / Monoacylglycerol Lipases (NLM Chemicals)},
cin = {EMBL(-2012)},
ddc = {570},
cid = {$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {DORIS Beamline D1.2 (POF2-54G13)},
pid = {G:(DE-H253)POF2-D1.2-20130405},
experiment = {EXP:(DE-H253)D-D1.2-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22561231},
UT = {WOS:000305359200009},
doi = {10.1016/j.bbalip.2012.04.006},
url = {https://bib-pubdb1.desy.de/record/141360},
}