3PE6

Crystal Structure of a soluble form of human MGLL in complex with an inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.147 
  • R-Value Work: 0.114 
  • R-Value Observed: 0.115 

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This is version 1.3 of the entry. See complete history


Literature

Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 A resolution.

Schalk-Hihi, C.Schubert, C.Alexander, R.Bayoumy, S.Clemente, J.C.Deckman, I.DesJarlais, R.L.Dzordzorme, K.C.Flores, C.M.Grasberger, B.Kranz, J.K.Lewandowski, F.Liu, L.Ma, H.Maguire, D.Macielag, M.J.McDonnell, M.E.Mezzasalma Haarlander, T.Miller, R.Milligan, C.Reynolds, C.Kuo, L.C.

(2011) Protein Sci 20: 670-683

  • DOI: https://doi.org/10.1002/pro.596
  • Primary Citation of Related Structures:  
    3PE6

  • PubMed Abstract: 

    A high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid-domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2-arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transform membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form.


  • Organizational Affiliation

    Department of Structural Biology, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, Spring House, Pennsylvania 19477, USA. cschalkh@its.jnj.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Monoglyceride lipase303Homo sapiensMutation(s): 3 
Gene Names: MGLLhCG_40840
EC: 3.1.1.23
Membrane Entity: Yes 
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
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZYH
Query on ZYH

Download Ideal Coordinates CCD File 
B [auth A](2-cyclohexyl-1,3-benzoxazol-6-yl){3-[4-(pyrimidin-2-yl)piperazin-1-yl]azetidin-1-yl}methanone
C25 H30 N6 O2
IABLYMUVWHQTGC-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.147 
  • R-Value Work: 0.114 
  • R-Value Observed: 0.115 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.947α = 90
b = 128.145β = 90
c = 60.602γ = 90
Software Package:
Software NamePurpose
StructureStudiodata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data 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: 2011-03-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2013-06-19
    Changes: Database references
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description