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PDBsum entry 1rm8

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protein ligands metals links
Hydrolase PDB id
1rm8
Jmol
Contents
Protein chain
169 a.a. *
Ligands
BAT
Metals
_ZN ×2
_CA ×2
Waters ×115
* Residue conservation analysis
PDB id:
1rm8
Name: Hydrolase
Title: Crystal structure of the catalytic domain of mmp-16/mt3- mmp: characterization of mt-mmp specific features
Structure: Matrix metalloproteinase-16. Chain: a. Fragment: catalytic domain. Synonym: mmp-16. Mt3-mmp. Membrane-type matrix metalloproteinase 3. Mt-mmp 3. Mtmmp3. Membrane-type-3 matrix metalloproteinase. Mt3mmp. Mmp-x2. Engineered: yes. Other_details: complexed with batimastat (bb94)
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
1.80Å     R-factor:   0.209     R-free:   0.236
Authors: R.Lang,M.Braun,N.E.Sounni,A Noel,F.Frankenne,J.-M.Foidart, W.Bode,K.Maskos
Key ref:
R.Lang et al. (2004). Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features. J Mol Biol, 336, 213-225. PubMed id: 14741217 DOI: 10.1016/j.jmb.2003.12.022
Date:
27-Nov-03     Release date:   09-Mar-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P51512  (MMP16_HUMAN) -  Matrix metalloproteinase-16
Seq:
Struc:
 
Seq:
Struc:
607 a.a.
169 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular matrix   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     metallopeptidase activity     3 terms  

 

 
DOI no: 10.1016/j.jmb.2003.12.022 J Mol Biol 336:213-225 (2004)
PubMed id: 14741217  
 
 
Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features.
R.Lang, M.Braun, N.E.Sounni, A.Noel, F.Frankenne, J.M.Foidart, W.Bode, K.Maskos.
 
  ABSTRACT  
 
Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong attention, because four of them can activate a key player in the tumor scenario, proMMP-2/progelatinase A. In addition to this indirect effect on the cellular environment, these MT-MMPs degrade extracellular matrix proteins, and their overproduction is associated with tumor growth. We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. CdMT3-MMP exhibits a classical MMP-fold with similarity to MT1-MMP. Nevertheless, it also shows unique properties such as a modified MT-specific loop and a closed S1' specificity pocket, which might help to design specific inhibitors. Some MT-MMP-specific features, derived from the crystal structures of MT-1-MMP determined previously and MT3-MMP, and revealed in recent mutagenesis experiments, explain the impaired interaction of the MT-MMPs with TIMP-1. Docking experiments with proMMP-2 show some exposed loops including the MT-loop of cdMT3-MMP involved in the interaction with the proMMP-2 prodomain in the activation encounter complex. This model might help to understand the experimentally proven importance of the MT-loop for the activation of proMMP-2.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Stereo view toward the active site. (a) Protein residues and the batimastat inhibitor are shown as white (carbon atoms) and yellow (carbon atoms) sticks, respectively. Sulfur atoms are depicted in green, while zinc and calcium ions are represented by pink and blue spheres, respectively. The 2F[o]-F[c] simulated annealing omit map of batimastat is contoured at 1s. (b) and (c) The protein surfaces of MT3-MMP (b) and MT1-MMP (c) are shown as solid surfaces, colored according to negative (red) and positive (blue) electrostatic surface potential. The catalytic zinc ion is partially exposed (central pink sphere). The bound batimastat inhibitor of cdMT3-MMP is shown with atom colors (green carbon atoms), while the bound TIMP-2 is removed from the cdMT1-MMP/TIMP-2 complex.[25.] In contrast to the continuous S1' tube (to the right of the catalytic zinc, (c)) of MT1-MMP, the S1' specificity pocket of cdMT3-MMP is blocked. Figures were made with Swiss PDBViewer [75.] and PoV-Ray /MegaPov.
Figure 3.
Figure 3. (a) Model of the encounter complex between cdMT3-MMP and proMMP-2. MT3-MMP is shown as orange ribbon with the MT-loop in surface representation and the zinc and calcium ions in pink and green, respectively. The MT-MMP cleavage site of the prodomain (grey) of proMMP-2 (PDB code: 1CK7) was modeled into the active site of MT3-MMP (see the text). The catalytic domain, the fibronectin type-II repeats, the linker and the hemopexin-like domain are shown in green, purple, blue and yellow, respectively. The Figure was made with DS ViewerPro (Accelrys Inc.). (b) and (c) Stereo view of the experimental complex formed between cdMT1-MMP (blue) and TIMP-2[25.] (gray) and a modeled (hypothetical) complex formed between cdMT3-MMP (yellow) and TIMP-1 (red). The position of TIMP-1 was obtained by superimposing the experimental cdMMP-3/TIMP-1 complex [59.] on the cdMT1-MMP/TIMP-2 complex on the basis of the MMPs. Finally, cdMMP-3 was deleted and cdMT3-MMP was superimposed on cdMT1-MMP (b) both complexes are shown with their front side, the active site clefts point toward the bottom. The sA-sB and sG-sH loops of TIMP have been labeled, and the sV-hB loops and the MT-loops of the MT-MMPs have been indicated. The Figure has been made with Swiss PDBViewer , /-. [75.] (c) Stereo view of the close-up of the central TIMP binding site of the experimental cdMT1-MMP (blue)-TIMP2 (gray) complex and the modeled cdMT3-MMP (orange)-TIMP-1 (green) complex. The Figure was made with DS ViewerPro (Accelrys Inc.).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 336, 213-225) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19217394 A.R.Kinjo, and H.Nakamura (2009).
Comprehensive structural classification of ligand-binding motifs in proteins.
  Structure, 17, 234-246.  
17660250 A.B.Hamze, S.Wei, H.Bahudhanapati, S.Kota, K.R.Acharya, and K.Brew (2007).
Constraining specificity in the N-domain of tissue inhibitor of metalloproteinases-1; gelatinase-selective inhibitors.
  Protein Sci, 16, 1905-1913.  
16261161 R.Djafarzadeh, E.Noessner, H.Engelmann, D.J.Schendel, M.Notohamiprodjo, I.von Luettichau, and P.J.Nelson (2006).
GPI-anchored TIMP-1 treatment renders renal cell carcinoma sensitive to FAS-meditated killing.
  Oncogene, 25, 1496-1508.  
16142437 J.F.Porter, S.Sharma, D.L.Wilson, M.A.Kappil, R.P.Hart, and D.T.Denhardt (2005).
Tissue inhibitor of metalloproteinases-1 stimulates gene expression in MDA-MB-435 human breast cancer cells by means of its ability to inhibit metalloproteinases.
  Breast Cancer Res Treat, 94, 185-193.  
15780640 P.Patwari, G.Gao, J.H.Lee, A.J.Grodzinsky, and J.D.Sandy (2005).
Analysis of ADAMTS4 and MT4-MMP indicates that both are involved in aggrecanolysis in interleukin-1-treated bovine cartilage.
  Osteoarthritis Cartilage, 13, 269-277.  
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.