3B2Z

Crystal Structure of ADAMTS4 (apo form)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.312 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.257 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.

Mosyak, L.Georgiadis, K.Shane, T.Svenson, K.Hebert, T.McDonagh, T.Mackie, S.Olland, S.Lin, L.Zhong, X.Kriz, R.Reifenberg, E.L.Collins-Racie, L.A.Corcoran, C.Freeman, B.Zollner, R.Marvell, T.Vera, M.Sum, P.E.Lavallie, E.R.Stahl, M.Somers, W.

(2008) Protein Sci 17: 16-21

  • DOI: https://doi.org/10.1110/ps.073287008
  • Primary Citation of Related Structures:  
    2RJP, 2RJQ, 3B2Z

  • PubMed Abstract: 

    Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor-bound enzymes exhibit two essentially different catalytic-site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.


  • Organizational Affiliation

    Department of Chemical and Screening Sciences, Wyeth Research, Cambridge, MA 02140, USA. lmosyak@wyeth.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ADAMTS-4
A, B, C, D, E
A, B, C, D, E, F, G, H
316Homo sapiensMutation(s): 1 
Gene Names: ADAMTS4KIAA0688
EC: 3.4.24.82
UniProt & NIH Common Fund Data Resources
Find proteins for O75173 (Homo sapiens)
Explore O75173 
Go to UniProtKB:  O75173
PHAROS:  O75173
GTEx:  ENSG00000158859 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75173
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
AA [auth G]
DA [auth H]
I [auth A]
L [auth B]
O [auth C]
AA [auth G],
DA [auth H],
I [auth A],
L [auth B],
O [auth C],
R [auth D],
U [auth E],
X [auth F]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
BA [auth G]
CA [auth G]
EA [auth H]
FA [auth H]
J [auth A]
BA [auth G],
CA [auth G],
EA [auth H],
FA [auth H],
J [auth A],
K [auth A],
M [auth B],
N [auth B],
P [auth C],
Q [auth C],
S [auth D],
T [auth D],
V [auth E],
W [auth E],
Y [auth F],
Z [auth F]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.312 
  • R-Value Work: 0.254 
  • R-Value Observed: 0.257 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.33α = 90
b = 84.315β = 112.23
c = 150.146γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-08-30
    Changes: Data collection, Refinement description