3E8R

Crystal structure of catalytic domain of TACE with hydroxamate inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.

Mazzola, R.D.Zhu, Z.Sinning, L.McKittrick, B.Lavey, B.Spitler, J.Kozlowski, J.Neng-Yang, S.Zhou, G.Guo, Z.Orth, P.Madison, V.Sun, J.Lundell, D.Niu, X.

(2008) Bioorg Med Chem Lett 18: 5809-5814

  • DOI: https://doi.org/10.1016/j.bmcl.2008.09.045
  • Primary Citation of Related Structures:  
    3E8R, 3EDZ

  • PubMed Abstract: 

    A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1'-S3' pocket.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Schering Plough Research Institute, Kenilworth, NJ 07033, USA. robert.mazzola@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ADAM 17
A, B
271Homo sapiensMutation(s): 3 
Gene Names: ADAM17CSVPTACE
EC: 3.4.24.86
UniProt & NIH Common Fund Data Resources
Find proteins for P78536 (Homo sapiens)
Explore P78536 
Go to UniProtKB:  P78536
PHAROS:  P78536
GTEx:  ENSG00000151694 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP78536
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
615
Query on 615

Download Ideal Coordinates CCD File 
D [auth A],
G [auth B]
(1R,2S)-N~2~-hydroxy-1-{4-[(2-phenylquinolin-4-yl)methoxy]benzyl}cyclopropane-1,2-dicarboxamide
C28 H25 N3 O4
BKHGWMSYWJIRLD-LXFBAYGMSA-N
INN
Query on INN

Download Ideal Coordinates CCD File 
E [auth A]N-{(2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}-3-methyl-L-valyl-N-(2-aminoethyl)-L-alaninamide
C19 H37 N5 O5
LMIQCBIEAHJAMZ-GZBFAFLISA-N
CIT
Query on CIT

Download Ideal Coordinates CCD File 
H [auth B]CITRIC ACID
C6 H8 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
615 PDBBind:  3E8R Ki: 0.18 (nM) from 1 assay(s)
BindingDB:  3E8R Ki: min: 0.18, max: 0.18 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.190 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.722α = 90
b = 75.761β = 90
c = 102.985γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2008-10-21 
  • Deposition Author(s): Orth, P.

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2013-02-27
    Changes: Other
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations