Structure and Dynamics of an Archeal Monoglyceride Lipase from Palaeococcus ferrophilus as Revealed by Crystallography and In Silico Analysis.

Geoffray Labar,Amaury Flaba,Laurence Leherte,Johan Wouters,Nathalie Brandt

doi:10.3390/biom11040533

Abstract

The crystallographic analysis of a lipase from Palaeococcus ferrophilus (PFL) previously annotated as a lysophospholipase revealed high structural conservation with other monoglyceride lipases, in particular in the lid domain and substrate binding pockets. In agreement with this observation, PFL was shown to be active on various monoacylglycerols. Molecular Dynamics (MD) studies performed in the absence and in the presence of ligands further allowed characterization of the dynamics of this system and led to a systematic closure of the lid compared to the crystal structure. However, the presence of ligands in the acyl-binding pocket stabilizes intermediate conformations compared to the crystal and totally closed structures. Several lid-stabilizing or closure elements were highlighted, i.e., hydrogen bonds between Ser117 and Ile204 or Asn142 and its facing amino acid lid residues, as well as Phe123. Thus, based on this complementary crystallographic and MD approach, we suggest that the crystal structure reported herein represents an open conformation, at least partially, of the PFL, which is likely stabilized by the ligand, and it brings to light several key structural features prone to participate in the closure of the lid.

Highlights

Lipases and esterases are of great value as biocatalysists in diverse industrial applications
Since the enzyme was shown to constitute a key actor of the endocannabinoid signaling system, a great deal of attention was devoted to the human monoglyceride lipase, which is considered as a promising drug target for the treatment of several
Palaeococcus ferrophilus (PFL) was expressed in E. coli and purified by affinity chromatography and gel filtration

Summary

Introduction

Lipases and esterases are of great value as biocatalysists in diverse industrial applications. Esterification, transesterification, or hydrolysis by lipases allow the synthesis or degradation of a wide range of compounds of interest in the pharmaceutical, food, textile, or paper industries, as well as in environmental applications for the synthesis and recycling of biodegradable polymers [1,2,3,4]. They are in use as biocatalysts for the production of biodiesels, which are an important renewable fuel source [2,4,5]. Since the enzyme was shown to constitute a key actor of the endocannabinoid signaling system, a great deal of attention was devoted to the human monoglyceride lipase (hMGL), which is considered as a promising drug target for the treatment of several

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Discussion

Conclusion