The structure of monoacylglycerol lipase from Bacillus sp. H257 reveals unexpected conservation of the cap architecture between bacterial and human enzymes.

Biochimica Et Biophysica Acta
Srinivasan RengachariMonika Oberer

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...Continue Reading

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Citations

Sep 10, 2013·The Journal of Biological Chemistry·Srinivasan RengachariMonika Oberer
Jun 5, 2014·Journal of Structural and Functional Genomics·Toshiharu Tsurumura, Hideaki Tsuge
May 21, 2013·Microbiological Research·Yanbing ZhuLuhong Hou
Mar 19, 2016·FEBS Letters·Kandasamy SelvarajuVasanthi Nachiappan
Jan 31, 2018·Scientific Reports·Sergiy TyukhtenkoAlexandros Makriyannis
Mar 14, 2020·Journal of Lipid Research·Hyo Jung KimAe-Ran Kwon
Feb 11, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Srinivasan RengachariMonika Oberer
Mar 25, 2017·Frontiers in Bioengineering and Biotechnology·Faez Iqbal KhanYonghua Wang
Nov 20, 2020·Biology·James BirchAndrew Quigley

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Methods Mentioned

BETA
X-ray

Software Mentioned

Dali
PRIMUS
CRYSOL
MOLE
iMosflm
Vasco
REFMAC5
PHENIX
GROMACS
MGL

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