1D8M

CRYSTAL STRUCTURE OF MMP3 COMPLEXED WITH A HETEROCYCLE-BASED INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.44 Å
  • R-Value Free: 0.315 
  • R-Value Work: 0.277 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Heterocycle-based MMP inhibitors with P2' substituents.

Pikul, S.Dunham, K.M.Almstead, N.G.De, B.Natchus, M.G.Taiwo, Y.O.Williams, L.E.Hynd, B.A.Hsieh, L.C.Janusz, M.J.Gu, F.Mieling, G.E.

(2001) Bioorg Med Chem Lett 11: 1009-1013

  • DOI: https://doi.org/10.1016/s0960-894x(01)00137-8
  • Primary Citation of Related Structures:  
    1D8M, 1G05

  • PubMed Abstract: 

    Potent and selective inhibition of matrix metalloproteinases was demonstrated for a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2' substituent that can be modified. Binding interactions of this substituent at the S2' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series.


  • Organizational Affiliation

    Procter and Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA. spikul@avalonrx.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
STROMELYSIN-1 PRECURSOR
A, B
173Homo sapiensMutation(s): 0 
EC: 3.4.24.17
UniProt & NIH Common Fund Data Resources
Find proteins for P08254 (Homo sapiens)
Explore P08254 
Go to UniProtKB:  P08254
PHAROS:  P08254
GTEx:  ENSG00000149968 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08254
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BBH
Query on BBH

Download Ideal Coordinates CCD File 
M [auth B]1-BENZYL-3-(4-METHOXY-BENZENESULFONYL)-6-OXO-HEXAHYDRO-PYRIMIDINE-4-CARBOXYLIC ACID HYDROXYAMIDE
C19 H21 N3 O6 S
SUSMVCKSLVPRCL-QGZVFWFLSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth B],
I [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
J [auth B]
K [auth B]
E [auth A],
F [auth A],
G [auth A],
J [auth B],
K [auth B],
L [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
BBH PDBBind:  1D8M IC50: 3.1 (nM) from 1 assay(s)
BindingDB:  1D8M IC50: 3.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.44 Å
  • R-Value Free: 0.315 
  • R-Value Work: 0.277 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.96α = 90
b = 78.59β = 90
c = 105.93γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-10-25
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations