Monoglyceride lipase

Basic Information
Short Name	MgII, MGL
UNP ID	Q8R431
Organism	Rattus norvegicus
Cys Site	Cys208
Family/Domain	Serine aminopeptidase, S33, AB hydrolase superfamily, Monoacylglycerol lipase family
Known Ligand	Ligand list
Function Type	Metabolic enzyme

Summary

Protein Function

Monoacylglycerol lipase (MGL) is a cytosolic serine hydrolase that cleaves monoacylglycerols into fatty acid and glycerol through a catalytic mechanism that involves a classical serine-aspartate-histidine triad. MGL is a member of the α/β-hydrolase family of enzymes and is distantly related to microbial lysophospholipases and haloperoxidases. Because of its abundant expression in mammals in lipid-metabolizing tissues, such as white fat and liver, MGL is thought to catalyse the final step of the lipolytic cascade that releases fatty acids from triacylglycerol stores. In the brain, however, a primary role of MGL may be to carry out the hydrolysis and inactivation of the endocannabinoid neurotransmitter, 2-arachidonoyl-sn-glycerol (2-AG). (PMID: 19486005)

Cys Function & Property

Residues Cys201 and Cys208 are located within the lid domain, wherefrom they might be able to extend their sulphydryl groups towards the substrate-binding site, while residues Cys32 and Cys55 are positioned in two structurally conserved regions: Cys32 in the second beta-strand and Cys55 in a loop before the beginning of the first alpha-helix. Cys301 is not included in the model because it occupies a region of MGL that is not present in the chloroperoxidase template. (PMID: 19486005)

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The positions of active site His269 and cysteine reisudes in MGL structure

• Hydrophobic property:

• SASA:

Unknown

Protein Sequence

MPEASSPRRT PQNVPYQDLP HLVNADGQYL FCRYWKPSGT PKALIFVSHG
AGEHCGRYDE LAQMLKRLDM LVFAHDHVGH GQSEGERMVV SDFQVFVRDL
LQHVNTVQKD YPEVPVFLLG HSMGGAISIL AAAERPTHFS GMILISPLIL
ANPESASTLK VLAAKLLNFV LPNISLGRID SSVLSRNKSE VDLYNSDPLI
CHAGVKVCFG IQLLNAVSRV ERAMPRLTLP FLLLQGSADR LCDSKGAYLL
MESSPSQDKT LKMYEGAYHV LHKELPEVTN SVLHEINTWV SHRIAVAGAR
CLP

Structural Information

• Known structure with covalent ligand:
  

Unknown

• Protein structure:

Unknown

Related Pathway

• Glycerolipid metabolism
  
• Retrograde endocannabinoid signaling
  
• Regulation of lipolysis in adipocytes
  

Experimental Evidence

Cys-directed mutation, Homologous Analysis Of Sequence, Molecular Docking

Reference

1. King A R, Lodola A, Carmi C, et al. A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone‐based enzyme inhibitors[J]. British journal of pharmacology, 2009, 157(6): 974-983. 19486005