2ADU

Human Methionine Aminopeptidase Complex with 4-Aryl-1,2,3-triazole Inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.355 
  • R-Value Work: 0.335 
  • R-Value Observed: 0.335 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history. 


Literature

4-Aryl-1,2,3-triazole: A Novel Template for a Reversible Methionine Aminopeptidase 2 Inhibitor, Optimized To Inhibit Angiogenesis in Vivo

Kallander, L.S., Lu, Q., Chen, W., Tomaszek, T., Yang, G., Tew, D., Meek, T.D., Hofmann, G.A., Schulz-Pritchard, C.K., Smith, W.W., Janson, C.A., Ryan, M.D., Zhang, G.F., Johanson, K.O., Kirkpatrick, R.B., Ho, T.F., Fisher, P.W., Mattern, M.R., Johnson, R.K., Hansbury, M.J., Winkler, J.D., Ward, K.W., Veber, D.F., Thompson, S.K.

(2005) J Med Chem 48: 5644-5647

  • DOI: https://doi.org/10.1021/jm050408c
  • Primary Citation of Related Structures:  
    2ADU

  • PubMed Abstract: 

    Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo.

    • Organizational Affiliation: 

    GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. lara.s.kallander@gsk.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Methionine aminopeptidase 2369Homo sapiensMutation(s): 0 
Gene Names: METAP2, MNPEP, P67EIF2
EC: 3.4.11.18
UniProt & NIH Common Fund Data Resources
Find proteins for P50579 (Homo sapiens)
Explore P50579 
Go to UniProtKB:  P50579
PHAROS:  P50579
GTEx:  ENSG00000111142 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50579
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
R20
Query on R20
Download Ideal Coordinates CCD File 
D [auth A]4-(3-METHYLPHENYL)-1H-1,2,3-TRIAZOLE
C9 H9 N3
XQHCBHNLRWLGQS-UHFFFAOYSA-N
CO
Query on CO
Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]		COBALT (II) ION
Co
XLJKHNWPARRRJB-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
R20 BindingDB:  2ADU Ki: 18 (nM) from 1 assay(s)
IC50: 18 (nM) from 1 assay(s)
PDBBind:  2ADU Ki: 18 (nM) from 1 assay(s)
Binding MOAD:  2ADU Ki: 18 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.355 
  • R-Value Work: 0.335 
  • R-Value Observed: 0.335 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.819α = 90
b = 99.264β = 90
c = 101.282γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
CNSphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-09-13
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description