3DDF

GOLGI MANNOSIDASE II complex with (3R,4R,5R)-3,4-Dihydroxy-5-({[(1R)-2-hydroxy-1 phenylethyl]amino}methyl) pyrrolidin-2-one


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.151 
  • R-Value Work: 0.115 
  • R-Value Observed: 0.115 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Functionalized pyrrolidine inhibitors of human type II alpha-mannosidases as anti-cancer agents: optimizing the fit to the active site

Fiaux, H.Kuntz, D.A.Hoffman, D.Janzer, R.C.Gerber-Lemaire, S.Rose, D.R.Juillerat-Jeanneret, L.

(2008) Bioorg Med Chem 16: 7337-7346

  • DOI: https://doi.org/10.1016/j.bmc.2008.06.021
  • Primary Citation of Related Structures:  
    3DDF, 3DDG

  • PubMed Abstract: 

    Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi alpha-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of alpha-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.


  • Organizational Affiliation

    Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
alpha-mannosidase 21,045Drosophila melanogasterMutation(s): 1 
Gene Names: alpha-Man-IIGmII
EC: 3.2.1.114
UniProt
Find proteins for Q24451 (Drosophila melanogaster)
Explore Q24451 
Go to UniProtKB:  Q24451
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ24451
Glycosylation
Glycosylation Sites: 1Go to GlyGen: Q24451-1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GB6
Query on GB6

Download Ideal Coordinates CCD File 
D [auth A](3R,4R,5R)-3,4-dihydroxy-5-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)pyrrolidin-2-one
C13 H18 N2 O4
KRKSNZJFCXFNFF-WRWGMCAJSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
B [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
MPD
Query on MPD

Download Ideal Coordinates CCD File 
F [auth A](4S)-2-METHYL-2,4-PENTANEDIOL
C6 H14 O2
SVTBMSDMJJWYQN-YFKPBYRVSA-N
MRD
Query on MRD

Download Ideal Coordinates CCD File 
E [auth A](4R)-2-METHYLPENTANE-2,4-DIOL
C6 H14 O2
SVTBMSDMJJWYQN-RXMQYKEDSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
GB6 PDBBind:  3DDF Ki: 2.20e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.151 
  • R-Value Work: 0.115 
  • R-Value Observed: 0.115 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.923α = 90
b = 109.993β = 90
c = 138.909γ = 90
Software Package:
Software NamePurpose
SHELXL-97refinement
SCALEPACKdata scaling
CNSrefinement
SHELXrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
CNSphasing
DENZOdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2019-07-24
    Changes: Data collection, Derived calculations, Refinement description
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.5: 2023-08-30
    Changes: Data collection, Database references, Refinement description, Structure summary