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PDBsum entry 1zs0

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protein ligands metals links
Hydrolase PDB id
1zs0
Jmol PyMol
Contents
Protein chain
163 a.a. *
Ligands
EIN
MES
Metals
_CA ×2
_ZN ×2
Waters ×244
* Residue conservation analysis
PDB id:
1zs0
Name: Hydrolase
Title: Crystal structure of the complex between mmp-8 and a phosphonate inhibitor (s-enantiomer)
Structure: Neutrophil collagenase. Chain: a. Fragment: catalytic domain of neutrophil collagenase (residues:80-242). 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 bl21. Expression_system_taxid: 511693.
Resolution:
1.56Å     R-factor:   0.210     R-free:   0.235
Authors: G.Pochetti,E.Gavuzzo,C.Campestre,M.Agamennone,P.Tortorella, V.Consalvi,C.Gallina,O.Hiller,H.Tschesche,P.A.Tucker,F.Mazz
Key ref: G.Pochetti et al. (2006). Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. J Med Chem, 49, 923-931. PubMed id: 16451058 DOI: 10.1021/jm050787+
Date:
23-May-05     Release date:   02-May-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 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/jm050787+ J Med Chem 49:923-931 (2006)
PubMed id: 16451058  
 
 
Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates.
G.Pochetti, E.Gavuzzo, C.Campestre, M.Agamennone, P.Tortorella, V.Consalvi, C.Gallina, O.Hiller, H.Tschesche, P.A.Tucker, F.Mazza.
 
  ABSTRACT  
 
Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19204958 M.T.Rubino, M.Agamennone, C.Campestre, G.Fracchiolla, A.Laghezza, F.Loiodice, E.Nuti, A.Rossello, and P.Tortorella (2009).
Synthesis, SAR, and biological evaluation of alpha-sulfonylphosphonic acids as selective matrix metalloproteinase inhibitors.
  ChemMedChem, 4, 352-362.  
17477392 J.V.Edwards, and P.S.Howley (2007).
Human neutrophil elastase and collagenase sequestration with phosphorylated cotton wound dressings.
  J Biomed Mater Res A, 83, 446-454.  
16680577 J.F.Fisher, and S.Mobashery (2006).
Recent advances in MMP inhibitor design.
  Cancer Metastasis Rev, 25, 115-136.  
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.

 

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