Monoglyceride lipase (MGL), the main enzyme responsible for the hydrolytic deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), is an intracellular serine hydrolase that plays critical roles in many physiological and pathological processes, such as pain, inflammation, neuroprotection and cancer. The crystal structures of MGL that are currently available provide valuable information about how this enzyme might function and interact with site-directed small-molecule inhibitors. On the other hand, its conformational equilibria and the contribution of regulatory cysteine residues present within the substrate-binding pocket or on protein surface remain open issues. Several classes of MGL inhibitors have been developed, from early reversible ones, such as URB602 and pristimerin, to carbamoylating agents that react with the catalytic serine, such as JZL184 and more recent O-hexafluoroisopropyl carbamates. Other inhibitors that modulate MGL activity by interacting with conserved regulatory cysteines act through mechanisms that deserve to be more thoroughly investigated.

Monoglyceride lipase: Structure and inhibitors / Scalvini, Laura; Piomelli, Daniele; Mor, Marco. - In: CHEMISTRY AND PHYSICS OF LIPIDS. - ISSN 0009-3084. - 197:(2016), pp. 13-24. [10.1016/j.chemphyslip.2015.07.011]

Monoglyceride lipase: Structure and inhibitors

SCALVINI, Laura;MOR, Marco
2016-01-01

Abstract

Monoglyceride lipase (MGL), the main enzyme responsible for the hydrolytic deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), is an intracellular serine hydrolase that plays critical roles in many physiological and pathological processes, such as pain, inflammation, neuroprotection and cancer. The crystal structures of MGL that are currently available provide valuable information about how this enzyme might function and interact with site-directed small-molecule inhibitors. On the other hand, its conformational equilibria and the contribution of regulatory cysteine residues present within the substrate-binding pocket or on protein surface remain open issues. Several classes of MGL inhibitors have been developed, from early reversible ones, such as URB602 and pristimerin, to carbamoylating agents that react with the catalytic serine, such as JZL184 and more recent O-hexafluoroisopropyl carbamates. Other inhibitors that modulate MGL activity by interacting with conserved regulatory cysteines act through mechanisms that deserve to be more thoroughly investigated.
2016
Monoglyceride lipase: Structure and inhibitors / Scalvini, Laura; Piomelli, Daniele; Mor, Marco. - In: CHEMISTRY AND PHYSICS OF LIPIDS. - ISSN 0009-3084. - 197:(2016), pp. 13-24. [10.1016/j.chemphyslip.2015.07.011]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2812377
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