(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Eukaryota: NE > Opisthokonta: NE > Metazoa: NE > Eumetazoa: NE > Bilateria: NE > Protostomia: NE > Spiralia: NE > Lophotrochozoa: NE > Annelida: NE > Clitellata: NE > Hirudinea: NE > Hirudinida: NE > Hirudiniformes: NE > Hirudinidae: NE > Hirudo: NE > Hirudo verbana: NE
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MDDQLMGQGRCADAHVFENTRGQKLSCKYWNSYNQQLRCLVFISHGVGEH SMCYNDMAKTLTEEGCTVFSHDHVGHGESEGTRVHIDDFSFYCDDVVAHV KKIKERHVNLPCFIIGHSMGGTVAIIAALKNPDLFSGVILISPAILADDR NVGSFKIFLARMAGKIWPSMQIGSISPEWLSRDAEICRKYVEDPLVWHGG LKARWACCMLDSMNYIQNNLEKITFPFLLLHGSEDKICQLQGSTLMLEKS SSTDKTLKVYQGAYHQVHHELAETEIEVLRDISKWIISRTSHASTEVYAK
Reference
Title: Characterization of a monoacylglycerol lipase in the medicinal leech, Hirudo verbana Kabeiseman E, Paulsen R, Burrell BD Ref: Comparative Biochemistry & Physiology B Biochem Mol Biol, 243-244:110433, 2020 : PubMed
Endocannabinoids are a class of lipid neuromodulators found throughout the animal kingdom. Among the endocannabinoids, 2-arachydonoyl glycerol (2-AG) is the most prevalent endocannabinoid and monoacylglycerol lipase (MAGL) is a serine hydrolase primarily responsible for metabolizing 2-AG in mammals. In the medicinal leech, Hirudo verbana, 2-AG has been found to be an important and multi-functional modulator of synaptic transmission and behavior. However, very little is known about the molecular components of its synthesis and degradation. In this study we have identified cDNA in Hirudo that encodes a putative MAGL (HirMAGL). The encoded protein exhibits considerable sequence and structural conservation with mammalian forms of MAGL, especially in the catalytic triad that mediates 2-AG metabolism. Additionally, HirMAGL transcripts are detected in the Hirudo central nervous system. When expressed in HEK 293 cells HirMAGL segregates to the plasma membrane as expected. It also exhibits serine hydrolase activity that is blocked when a critical active site residue is mutated. HirMAGL also demonstrates the capacity to metabolize 2-AG and this capacity is also prevented when the active site is mutated. Finally, HirMAGL activity is inhibited by JZL184 and MJN110, specific inhibitors of mammalian MAGL. To our knowledge these findings represent the first characterization of an invertebrate form of MAGL and show that HirMAGL exhibits many of the same properties as mammalian MAGL's that are responsible for 2-AG metabolism.
