1ZVX

Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (R-enantiomer)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.87 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates.

Pochetti, G.Gavuzzo, E.Campestre, C.Agamennone, M.Tortorella, P.Consalvi, V.Gallina, C.Hiller, O.Tschesche, H.Tucker, P.A.Mazza, F.

(2006) J Med Chem 49: 923-931

  • DOI: https://doi.org/10.1021/jm050787+
  • Primary Citation of Related Structures:  
    1ZS0, 1ZVX

  • PubMed 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.


  • Organizational Affiliation

    Istituto di Cristallografia, C.N.R., Monterotondo Stazione, Rome, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neutrophil collagenase163Homo sapiensMutation(s): 0 
Gene Names: MMP8CLG1
EC: 3.4.24.34
UniProt & NIH Common Fund Data Resources
Find proteins for P22894 (Homo sapiens)
Explore P22894 
Go to UniProtKB:  P22894
PHAROS:  P22894
GTEx:  ENSG00000118113 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22894
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
FIN PDBBind:  1ZVX Ki: 0.6 (nM) from 1 assay(s)
BindingDB:  1ZVX Ki: 0.6 (nM) from 1 assay(s)
IC50: 1.4 (nM) from 1 assay(s)
Binding MOAD:  1ZVX Ki: 0.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.87 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 32.706α = 90
b = 54.754β = 90
c = 68.413γ = 90
Software Package:
Software NamePurpose
MAR345data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2006-05-16
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Advisory, Refinement description
  • Version 1.4: 2018-01-24
    Changes: Database references
  • Version 1.5: 2023-08-23
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description