1GXD

proMMP-2/TIMP-2 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.333 
  • R-Value Work: 0.275 
  • R-Value Observed: 0.278 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural Insight Into the Complex Formation of Latent Matrix Metalloproteinase 2 with Tissue Inhibitor of Metalloproteinase 2

Morgunova, E.Tuuttila, A.Bergmann, U.Tryggvason, K.

(2002) Proc Natl Acad Sci U S A 99: 7414

  • DOI: https://doi.org/10.1073/pnas.102185399
  • Primary Citation of Related Structures:  
    1GXD

  • PubMed Abstract: 

    Matrix metalloproteinases (MMPs) are a family of multidomain enzymes involved in the physiological degradation of connective tissue, as well as in pathological states such as tumor invasion and arthritis. Apart from transcriptional regulation, MMPs are controlled by proenzyme activation and a class of specific tissue inhibitors of metalloproteinases (TIMPs) that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but it has also been implicated in a unique cell surface activation mechanism of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its binding to the hemopexin domain of proMMP-2 on the one hand and to a membrane-type MMP activator on the other. The present crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterized by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved.


  • Organizational Affiliation

    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
72 KDA TYPE IV COLLAGENASE
A, B
631Homo sapiensMutation(s): 1 
EC: 3.4.24.24
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P08253 (Homo sapiens)
Explore P08253 
Go to UniProtKB:  P08253
PHAROS:  P08253
GTEx:  ENSG00000087245 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08253
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
METALLOPROTEINASE INHIBITOR 2
C, D
194Homo sapiensMutation(s): 0 
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P16035 (Homo sapiens)
Explore P16035 
Go to UniProtKB:  P16035
PHAROS:  P16035
GTEx:  ENSG00000035862 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16035
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.333 
  • R-Value Work: 0.275 
  • R-Value Observed: 0.278 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.696α = 90
b = 374.575β = 90
c = 191γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
BLANCphasing
FFFEARphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-07-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2019-07-24
    Changes: Data collection
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description