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PDBsum entry 3dpe

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protein ligands metals links
Hydrolase PDB id
3dpe
Jmol
Contents
Protein chain
163 a.a. *
Ligands
AXB
Metals
_CA ×2
_ZN ×2
Waters ×216
* Residue conservation analysis
PDB id:
3dpe
Name: Hydrolase
Title: Crystal structure of the complex between mmp-8 and a non- zinc chelating inhibitor
Structure: Neutrophil collagenase. Chain: a. Fragment: mmp-8 catalytic domain, unp residues 100-262. Synonym: matrix metalloproteinase-8, mmp-8, pmnl collagenase, pmnl-cl. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mmp8, clg1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.60Å     R-factor:   0.210     R-free:   0.242
Authors: G.Pochetti,R.Montanari,F.Mazza
Key ref: G.Pochetti et al. (2009). Extra binding region induced by non-zinc chelating inhibitors into the S1' subsite of matrix metalloproteinase 8 (MMP-8). J Med Chem, 52, 1040-1049. PubMed id: 19173605 DOI: 10.1021/jm801166j
Date:
08-Jul-08     Release date:   03-Mar-09    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22894  (MMP8_HUMAN) -  Neutrophil collagenase
Seq:
Struc:
467 a.a.
163 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.34  - Neutrophil collagenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleavage of interstitial collagens in the triple helical domain. Unlike EC 3.4.24.7, this enzyme cleaves type III collagen more slowly than type I.
      Cofactor: Ca(2+); Zn(2+)
 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: 10.1021/jm801166j J Med Chem 52:1040-1049 (2009)
PubMed id: 19173605  
 
 
Extra binding region induced by non-zinc chelating inhibitors into the S1' subsite of matrix metalloproteinase 8 (MMP-8).
G.Pochetti, R.Montanari, C.Gege, C.Chevrier, A.G.Taveras, F.Mazza.
 
  ABSTRACT  
 
The mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21370305 H.S.Shieh, A.G.Tomasselli, K.J.Mathis, M.E.Schnute, S.S.Woodard, N.Caspers, J.M.Williams, J.R.Kiefer, G.Munie, A.Wittwer, A.M.Malfait, and M.D.Tortorella (2011).
Structure analysis reveals the flexibility of the ADAMTS-5 active site.
  Protein Sci, 20, 735-744.
PDB codes: 3ljt 3ljz
20481653 G.Dormán, S.Cseh, I.Hajdú, L.Barna, D.Kónya, K.Kupai, L.Kovács, and P.Ferdinandy (2010).
Matrix metalloproteinase inhibitors: a critical appraisal of design principles and proposed therapeutic utility.
  Drugs, 70, 949-964.  
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 codes are shown on the right.