2RJQ

Crystal structure of ADAMTS5 with inhibitor bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 2.1 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-5378Homo sapiensMutation(s): 0 
Gene Names: ADAMTS5ADAMTS11ADMP2
EC: 3.4.24
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UNA0 (Homo sapiens)
Explore Q9UNA0 
Go to UniProtKB:  Q9UNA0
PHAROS:  Q9UNA0
GTEx:  ENSG00000154736 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UNA0
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.231 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.471α = 90
b = 95.471β = 90
c = 93.487γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-08-30
    Changes: Data collection, Database references, Refinement description, Structure summary