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Proteinase inhibitor PDB id
1br9
Jmol
Contents
Protein chain
182 a.a. *
Waters ×63
* Residue conservation analysis
PDB id:
1br9
Name: Proteinase inhibitor
Title: Human tissue inhibitor of metalloproteinase-2
Structure: Metalloproteinase-2 inhibitor. Chain: a. Synonym: timp-2, tissue inhibitor of metalloproteinase-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: h5.
Biol. unit: Monomer (from PDB file)
Resolution:
2.10Å     R-factor:   0.238     R-free:   0.271
Authors: A.Tuuttila,E.Morgunova,U.Bergmann,Y.Lindqvist,K.Tryggvason, G.Schneider
Key ref:
A.Tuuttila et al. (1998). Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution. J Mol Biol, 284, 1133-1140. PubMed id: 9837731 DOI: 10.1006/jmbi.1998.2223
Date:
28-Aug-98     Release date:   04-May-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P16035  (TIMP2_HUMAN) -  Metalloproteinase inhibitor 2
Seq:
Struc: 		220 a.a.
182 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     negative regulation of cell proliferation   4 terms 
  Biochemical function     enzyme inhibitor activity     6 terms  

 

 
DOI no: 10.1006/jmbi.1998.2223 J Mol Biol 284:1133-1140 (1998)
PubMed id: 9837731  
 
 
Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution.
A.Tuuttila, E.Morgunova, U.Bergmann, Y.Lindqvist, K.Maskos, C.Fernandez-Catalan, W.Bode, K.Tryggvason, G.Schneider.
 
  ABSTRACT  
 
The three-dimensional structure of human tissue inhibitor of metalloproteinases-2 (TIMP-2) was determined by X-ray crystallography to 2.1 A resolution. The structure of the inhibitor consists of two domains. The N-terminal domain (residues 1-110) is folded into a beta-barrel, similar to the oligonucleotide/oligosaccharide binding fold otherwise found in certain DNA-binding proteins. The C-terminal domain (residues 111-194) contains a parallel stranded beta-hairpin plus a beta-loop-beta motif. Comparison of the structure of uncomplexed human TIMP-2 with that of bovine TIMP-2 bound to the catalytic domain of human MMP-14 suggests an internal rotation between the two domains of approximately 13 degrees upon binding to the protease. Furthermore, local conformational differences in the two structures that might be induced by formation of the protease-inhibitor complex have been found. The most prominent of these involves residues 27-40 of the A-B beta-hairpin loop. Structure-based alignment of amino acid sequences of representatives of the TIMP family maps the sequence differences mainly to loop regions, and some of these differences are proposed to be responsible for the particular properties of the various TIMP species.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Parts of the final 2F[o] - F[c] electron density map (contoured at 1.0s) showing a region of A and B strands from the b-barrel in the N-terminal domain. The refined model of TIMP-2 is superposed. 		Figure 5.
Figure 5. Stereo view of the superposition of the OB domains of the second subdomain of human single-stranded protein A (green) and the N-terminal domain of TIMP-2 (red).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 284, 1133-1140) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19656780 A.D.Kandasamy, A.K.Chow, M.A.Ali, and R.Schulz (2010).
Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix.
  Cardiovasc Res, 85, 413-423.  
20080133 K.Brew, and H.Nagase (2010).
The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity.
  Biochim Biophys Acta, 1803, 55-71.  
19550047 P.A.Arakaki, M.R.Marques, and M.C.Santos (2009).
MMP-1 polymorphism and its relationship to pathological processes.
  J Biosci, 34, 313-320.  
19025595 J.Melendez-Zajgla, L.Del Pozo, G.Ceballos, and V.Maldonado (2008).
Tissue inhibitor of metalloproteinases-4. The road less traveled.
  Mol Cancer, 7, 85.  
18612141 W.G.Stetler-Stevenson (2008).
Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities.
  Sci Signal, 1, re6.  
16421935 S.M.Park, I.K.Hwang, S.Y.Kim, S.J.Lee, K.S.Park, and S.T.Lee (2006).
Characterization of plasma gelsolin as a substrate for matrix metalloproteinases.
  Proteomics, 6, 1192-1199.  
15713681 M.H.Lee, M.Rapti, and G.Murphy (2005).
Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme.
  J Biol Chem, 280, 15967-15975.  
15036259 E.Lambert, E.Dassé, B.Haye, and E.Petitfrère (2004).
TIMPs as multifacial proteins.
  Crit Rev Oncol Hematol, 49, 187-198.  
15650352 R.Núñez Miguel, J.Sanders, J.Jeffreys, H.Depraetere, M.Evans, T.Richards, T.L.Blundell, B.Rees Smith, and J.Furmaniak (2004).
Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling.
  Thyroid, 14, 991.  
12670942 E.Liepinsh, L.Banyai, G.Pintacuda, M.Trexler, L.Patthy, and G.Otting (2003).
NMR structure of the netrin-like domain (NTR) of human type I procollagen C-proteinase enhancer defines structural consensus of NTR domains and assesses potential proteinase inhibitory activity and ligand binding.
  J Biol Chem, 278, 25982-25989.
PDB code: 1uap
12869573 M.H.Lee, M.Rapti, and G.Murphy (2003).
Unveiling the surface epitopes that render tissue inhibitor of metalloproteinase-1 inactive against membrane type 1-matrix metalloproteinase.
  J Biol Chem, 278, 40224-40230.  
12964975 R.N.Miguel, J.Sanders, J.Jeffreys, H.Depraetere, T.Blundell, J.Furmaniak, and B.Rees Smith (2003).
Thyrotropin receptor cleavage domain and tissue inhibitor of metalloproteinase-2.
  Thyroid, 13, 665-666.  
12486138 S.Bernocco, B.M.Steiglitz, D.I.Svergun, M.V.Petoukhov, F.Ruggiero, S.Ricard-Blum, C.Ebel, C.Geourjon, G.Deleage, B.Font, D.Eichenberger, D.S.Greenspan, and D.J.Hulmes (2003).
Low resolution structure determination shows procollagen C-proteinase enhancer to be an elongated multidomain glycoprotein.
  J Biol Chem, 278, 7199-7205.  
12515831 S.Wei, Y.Chen, L.Chung, H.Nagase, and K.Brew (2003).
Protein engineering of the tissue inhibitor of metalloproteinase 1 (TIMP-1) inhibitory domain. In search of selective matrix metalloproteinase inhibitors.
  J Biol Chem, 278, 9831-9834.  
12887053 W.Bode, and K.Maskos (2003).
Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases.
  Biol Chem, 384, 863-872.  
12032297 E.Morgunova, A.Tuuttila, U.Bergmann, and K.Tryggvason (2002).
Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2.
  Proc Natl Acad Sci U S A, 99, 7414-7419.
PDB code: 1gxd
12237470 M.H.Lee, K.Maskos, V.Knäuper, P.Dodds, and G.Murphy (2002).
Mapping and characterization of the functional epitopes of tissue inhibitor of metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: a new frontier in TIMP engineering.
  Protein Sci, 11, 2493-2503.  
10419448 H.Nagase, and J.F.Woessner (1999).
Matrix metalloproteinases.
  J Biol Chem, 274, 21491-21494.  
10415723 L.Blavier, P.Henriet, S.Imren, and Y.A.Declerck (1999).
Tissue inhibitors of matrix metalloproteinases in cancer.
  Ann N Y Acad Sci, 878, 108-119.  
10601286 R.A.Williamson, F.W.Muskett, M.J.Howard, R.B.Freedman, and M.D.Carr (1999).
The effect of matrix metalloproteinase complex formation on the conformational mobility of tissue inhibitor of metalloproteinases-2 (TIMP-2).
  J Biol Chem, 274, 37226-37232.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.