1ZXC

Crystal structure of catalytic domain of TNF-alpha converting enzyme (TACE) with inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.28 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.216 

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Ligand Structure Quality Assessment 


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


Literature

Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.

Levin, J.I., Chen, J.M., Laakso, L.M., Du, M., Du, X., Venkatesan, A.M., Sandanayaka, V., Zask, A., Xu, J., Xu, W., Zhang, Y., Skotnicki, J.S.

(2005) Bioorg Med Chem Lett 15: 4345-4349

  • DOI: https://doi.org/10.1016/j.bmcl.2005.06.072
  • Primary Citation of Related Structures:  
    1ZXC

  • PubMed Abstract: 

    The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.

    • Organizational Affiliation: 

    Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. levinji@wyeth.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ADAM 17
A, B
263Homo sapiensMutation(s): 2 
Gene Names: ADAM17, CSVP, TACE
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
Binding Affinity Annotations 
IDSourceBinding Affinity
IH6 PDBBind:  1ZXC IC50: 8 (nM) from 1 assay(s)
BindingDB:  1ZXC IC50: min: 8, max: 9 (nM) from 3 assay(s)
Binding MOAD:  1ZXC IC50: 8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.28 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.12α = 90
b = 59.17β = 90
c = 195.81γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-09-27
    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: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-23
    Changes: Data collection, Refinement description