3N2U

Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(4-methoxy-N(2-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)ethyl)phenylsulfonamido)acetamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.166 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).

Attolino, E.Calderone, V.Dragoni, E.Fragai, M.Richichi, B.Luchinat, C.Nativi, C.

(2010) Eur J Med Chem 45: 5919-5925

  • DOI: https://doi.org/10.1016/j.ejmech.2010.09.057
  • Primary Citation of Related Structures:  
    3N2U, 3N2V

  • PubMed Abstract: 

    N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.


  • Organizational Affiliation

    ProtEra s.r.l. viale delle Idee, 22 I-50019 Sesto F.no (FI), Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Macrophage metalloelastase158Homo sapiensMutation(s): 1 
Gene Names: MMP12HME
EC: 3.4.24.65
UniProt & NIH Common Fund Data Resources
Find proteins for P39900 (Homo sapiens)
Explore P39900 
Go to UniProtKB:  P39900
PHAROS:  P39900
GTEx:  ENSG00000262406 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP39900
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
D3X BindingDB:  3N2U Ki: min: 14, max: 14.3 (nM) from 2 assay(s)
PDBBind:  3N2U Ki: 14.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.166 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.394α = 90
b = 60.446β = 114.67
c = 54.043γ = 90
Software Package:
Software NamePurpose
CrysalisProdata collection
MOLREPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-11-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description