3JWE

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.196 

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This is version 1.2 of the entry. See complete history


Literature

Structural basis for human monoglyceride lipase inhibition.

Bertrand, T.Auge, F.Houtmann, J.Rak, A.Vallee, F.Mikol, V.Berne, P.F.Michot, N.Cheuret, D.Hoornaert, C.Mathieu, M.

(2010) J Mol Biol 396: 663-673

  • DOI: https://doi.org/10.1016/j.jmb.2009.11.060
  • Primary Citation of Related Structures:  
    3JW8, 3JWE

  • 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.


  • Organizational Affiliation

    Department of Structural Biology, Sanofi-Aventis, 13 Quai Jules Guesde, 94403 Vitry-sur-Seine cedex, France. thomas.bertrand@sanofi-aventis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MGLL protein
A, B
320Homo sapiensMutation(s): 0 
Gene Names: MGLLhCG_40840
EC: 3.1.1.23
UniProt & NIH Common Fund Data Resources
Find proteins for Q99685 (Homo sapiens)
Explore Q99685 
Go to UniProtKB:  Q99685
PHAROS:  Q99685
GTEx:  ENSG00000074416 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99685
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
F4P BindingDB:  3JWE IC50: min: 0.85, max: 0.9 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.196 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 87.821α = 90
b = 138.506β = 90
c = 127.381γ = 90
Software Package:
Software NamePurpose
DNAdata collection
MOLREPphasing
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description