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3JWE

Crystal structure of human mono-glyceride lipase in complex with SAR629

Summary for 3JWE
Entry DOI10.2210/pdb3jwe/pdb
DescriptorMGLL protein, 1-[bis(4-fluorophenyl)methyl]-4-(1H-1,2,4-triazol-1-ylcarbonyl)piperazine (3 entities in total)
Functional Keywordsalpha-beta hydrolase, hydrolase
Biological sourceHomo sapiens (human)
Total number of polymer chains2
Total formula weight71735.21
Authors
Bertrand, T.,Auge, F.,Houtmann, J.,Rak, A.,Vallee, F.,Mikol, V.,Berne, P.F.,Michot, N.,Cheuret, D.,Hoornaert, C.,Mathieu, M. (deposition date: 2009-09-18, release date: 2010-01-26, Last modification date: 2023-09-06)
Primary citationBertrand, T.,Auge, F.,Houtmann, J.,Rak, A.,Vallee, F.,Mikol, V.,Berne, P.F.,Michot, N.,Cheuret, D.,Hoornaert, C.,Mathieu, M.
Structural basis for human monoglyceride lipase inhibition.
J.Mol.Biol., 396:663-673, 2010
Cited by
PubMed Abstract: Monoglyceride lipase (MGL) is a serine hydrolase that hydrolyses 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. 2-AG is an endogenous ligand of cannabinoid receptors, involved in various physiological processes in the brain. We present here the first crystal structure of human MGL in its apo form and in complex with the covalent inhibitor SAR629. MGL shares the classic fold of the alpha/beta hydrolase family but depicts an unusually large hydrophobic occluded tunnel with a highly flexible lid at its entry and the catalytic triad buried at its end. Structures reveal the configuration of the catalytic triad and the shape and nature of the binding site of 2-AG. The bound structure of SAR629 highlights the key interactions for productive binding with MGL. The shape of the tunnel suggests a high druggability of the protein and provides an attractive template for drug discovery.
PubMed: 19962385
DOI: 10.1016/j.jmb.2009.11.060
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.7 Å)
Structure validation

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