کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1253283 1496280 2016 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Monoglyceride lipase: Structure and inhibitors
ترجمه فارسی عنوان
لیپاز مونوگلیسیرید: ساختار و مهار کننده ها
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی (عمومی)
چکیده انگلیسی


• Monoglyceride lipase (MGL) is the main responsible for degradation of 2-arachidonoylglycerol, the major endocannabinoid.
• Available crystal structures of MGL are here described, with focus on the role of the flexible lid domain.
• Different inhibitors of MGL have been reported. They can address the catalytic site or regulatory cysteines on the anzyme surface.

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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemistry and Physics of Lipids - Volume 197, May 2016, Pages 13–24
نویسندگان
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