PDBsum entry 1d2b

Go to PDB code: 
protein links
Hydrolase inhibitor PDB id
Protein chain
126 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase inhibitor
Title: The mmp-inhibitory, n-terminal domain of human tissue inhibitor of metalloproteinases-1 (n-timp-1), solution nmr, 29 structures
Structure: Tissue inhibitor of metalloproteinases-1. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: extracellular matrix. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: this is the first 126 residues of the full length of 184 residues naturally occurring in humans. The 126 residue recombinant n-terminal domain lacks the
NMR struc: 29 models
Authors: B.Wu,S.Arumugam,V.Semenchenko,K.Brew,S.R.Van Doren
Key ref:
B.Wu et al. (2000). NMR structure of tissue inhibitor of metalloproteinases-1 implicates localized induced fit in recognition of matrix metalloproteinases. J Mol Biol, 295, 257-268. PubMed id: 10623524 DOI: 10.1006/jmbi.1999.3362
22-Sep-99     Release date:   22-Dec-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01033  (TIMP1_HUMAN) -  Metalloproteinase inhibitor 1
207 a.a.
126 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     metalloendopeptidase inhibitor activity     1 term  


DOI no: 10.1006/jmbi.1999.3362 J Mol Biol 295:257-268 (2000)
PubMed id: 10623524  
NMR structure of tissue inhibitor of metalloproteinases-1 implicates localized induced fit in recognition of matrix metalloproteinases.
B.Wu, S.Arumugam, G.Gao, G.I.Lee, V.Semenchenko, W.Huang, K.Brew, S.R.Van Doren.
A high quality solution structure of the matrix metalloproteinase inhibitory N-terminal domain of recombinant human tissue inhibitor of metalloproteinases-1 (N-TIMP-1) has been determined. For the rigidly packed residues, the average RMSD to the mean structure is 0. 57 A for the backbone atoms and 1.00 A for all heavy atoms. Comparison of the solution structure of free N-TIMP-1 with the crystal structure of TIMP-1 bound to the catalytic domain of MMP-3 ( Gomis-R]uth et al., 1997 ) shows that the structural core of the beta barrel flanked by helices is nearly unchanged by the association with MMP-3, evident from a backbone RMSD of 1.15 A. However, clear differences in the conformation of the MMP-binding ridge of free and MMP-bound TIMP-1 suggest induced fit throughout the ridge. The MMP-dependent conformational changes in the ridge include a dramatic bending of AB loop residues Glu28 through Leu34, moderate hinge bending of the CD-loop about residues Ala65 and Cys70, and modest bending of the Cys1 through Pro6 segment. A large number of interresidue Nuclear Overhauser enhancements (NOEs) augmented by stereospecific assignments, torsion restraints, and dipolar couplings (an average of 18 non-trivial restraints per residue) engender confidence in these structural inferences. A tight cluster of three lysine residues and one arginine residue atop beta-strands A and B, and identical among TIMP sequences, form the heart of a highly conserved electropositive patch that may interact with anionic components of the extracellular matrix.
  Selected figure(s)  
Figure 2.
Figure 2. Superposition of free human N-TIMP-1 NMR model with free human N-TIMP-2 X-ray and NMR models. Representative N-TIMP-1 NMR model 22 was superimposed on TIMP-2 (1br9) [Tuuttila et al 1998]. The backbone atoms of TIMP-1 residues P6-E28, T33-G48, A56-P64, V69-S76 and N78-T121 were superimposed on the backbone atoms of TIMP-2 residues V6-E28, I40-G55, K58-A66, V71-I78, G80-N93, K95-H123. Representative N-TIMP-2 NMR model 3 (2tmp; broken lines) [Muskett et al 1998] was superimposed on the X-ray model of TIMP-2 (1br9; continuous line), using the same TIMP-2 residues listed above. N-TIMP-1 (NMR) is displayed with green cylinders, the N-terminal domain of full-length TIMP-2 (X-ray) with red cylinders and N-TIMP-2 (NMR) with red broken lines which become solid at the termini.
Figure 4.
Figure 4. Surface of the MMP-binding ridge of the free N-TIMP-1 NMR structure color-coded for (a) hydropathy and charge and (b) sequence identity, based on the alignment of 17 different TIMP-1, -2, -3 and -4 sequences [Douglas et al 1997]. The molecular surface was generated by rolling a sphere of 1.4 Å radius across the heavy atoms of representative NMR model 22 using GRASP [Nicholls et al 1991].
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 295, 257-268) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19574232 J.L.Lauer-Fields, M.J.Chalmers, S.A.Busby, D.Minond, P.R.Griffin, and G.B.Fields (2009).
Identification of specific hemopexin-like domain residues that facilitate matrix metalloproteinase collagenolytic activity.
  J Biol Chem, 284, 24017-24024.  
19564956 K.M.Guardino, S.R.Sheftic, R.E.Slattery, and A.T.Alexandrescu (2009).
Relative Stabilities of Conserved and Non-Conserved Structures in the OB-Fold Superfamily.
  Int J Mol Sci, 10, 2412-2430.  
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.  
18414739 R.A.Williamson, P.Panagiotidou, J.D.Mott, and M.J.Howard (2008).
Dynamic characterisation of the netrin-like domain of human type 1 procollagen C-proteinase enhancer and comparison to the N-terminal domain of tissue inhibitor of metalloproteinases (TIMP).
  Mol Biosyst, 4, 417-425.  
18615493 S.R.Van Doren, S.Wei, G.Gao, B.B.DaGue, M.O.Palmier, H.Bahudhanapati, and K.Brew (2008).
Inactivation of N-TIMP-1 by N-terminal acetylation when expressed in bacteria.
  Biopolymers, 89, 960-968.  
17050530 S.Iyer, S.Wei, K.Brew, and K.R.Acharya (2007).
Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1.
  J Biol Chem, 282, 364-371.
PDB code: 2j0t
14744980 Y.Qu, J.T.Guo, V.Olman, and Y.Xu (2004).
Protein structure prediction using sparse dipolar coupling data.
  Nucleic Acids Res, 32, 551-561.  
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.  
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.  
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.