3L0V

Crystal structure of catalytic domain of TACE with the first hydantoin inhibitor occupying the S1' pocket


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.189 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery and SAR of hydantoin TACE inhibitors.

Yu, W.Guo, Z.Orth, P.Madison, V.Chen, L.Dai, C.Feltz, R.J.Girijavallabhan, V.M.Kim, S.H.Kozlowski, J.A.Lavey, B.J.Li, D.Lundell, D.Niu, X.Piwinski, J.J.Popovici-Muller, J.Rizvi, R.Rosner, K.E.Shankar, B.B.Shih, N.Y.Siddiqui, M.A.Sun, J.Tong, L.Umland, S.Wong, M.K.Yang, D.Y.Zhou, G.

(2010) Bioorg Med Chem Lett 20: 1877-1880

  • DOI: https://doi.org/10.1016/j.bmcl.2010.01.148
  • Primary Citation of Related Structures:  
    3L0T, 3L0V

  • PubMed Abstract: 

    We disclose inhibitors of TNF-alpha converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA. wensheng.yu@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Disintegrin and metalloproteinase domain-containing protein 17
A, B
270Homo 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
Binding Affinity Annotations 
IDSourceBinding Affinity
724 BindingDB:  3L0V Ki: 23 (nM) from 1 assay(s)
Binding MOAD:  3L0V Ki: 23 (nM) from 1 assay(s)
PDBBind:  3L0V Ki: 23 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.189 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.038α = 90
b = 76.836β = 90
c = 103.798γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
AMoREphasing
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-03-02 
  • Deposition Author(s): Orth, P.

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-09-06
    Changes: Data collection, Refinement description