3I7I

MMP-13 in complex with a non zinc-chelating inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.314 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.235 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Improving potency and selectivity of a new class of non-Zn-chelating MMP-13 inhibitors.

Heim-Riether, A., Taylor, S.J., Liang, S., Gao, D.A., Xiong, Z., Michael August, E., Collins, B.K., Farmer, B.T., Haverty, K., Hill-Drzewi, M., Junker, H.D., Mariana Margarit, S., Moss, N., Neumann, T., Proudfoot, J.R., Keenan, L.S., Sekul, R., Zhang, Q., Li, J., Farrow, N.A.

(2009) Bioorg Med Chem Lett 19: 5321-5324

  • DOI: https://doi.org/10.1016/j.bmcl.2009.07.151
  • Primary Citation of Related Structures:  
    3I7G, 3I7I

  • PubMed Abstract: 

    Discovery and optimization of potency and selectivity of a non-Zn-chelating MMP-13 inhibitor with the aid of protein co-crystal structural information is reported. This inhibitor was observed to have a binding mode distinct from previously published MMP-13 inhibitors. Potency and selectivity were improved by extending the hit structure out from the active site into the S1' pocket.

    • Organizational Affiliation: 

    Boehringer Ingelheim Pharmaceuticals, Department of Medicinal Chemistry, 900 Ridgebury Rd, Ridgefield, CT 06877, USA. alexander.heim-riether@boehringer-ingelheim.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Collagenase 3
A, B
171Homo sapiensMutation(s): 0 
Gene Names: MMP13
EC: 3.4.24
UniProt & NIH Common Fund Data Resources
Find proteins for P45452 (Homo sapiens)
Explore P45452 
Go to UniProtKB:  P45452
PHAROS:  P45452
GTEx:  ENSG00000137745 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45452
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
518
Query on 518
Download Ideal Coordinates CCD File 
H [auth A]N-[4-(5-{[(1S)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]carbamoyl}furan-2-yl)phenyl]-1-benzofuran-2-carboxamide
C29 H29 N3 O5
JFDVHGPZDKQUGQ-SANMLTNESA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
I [auth B],
J [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]
K [auth B]
L [auth B]
E [auth A],
F [auth A],
G [auth A],
K [auth B],
L [auth B],
M [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
518 BindingDB:  3I7I IC50: 620 (nM) from 1 assay(s)
Binding MOAD:  3I7I IC50: 620 (nM) from 1 assay(s)
PDBBind:  3I7I IC50: 620 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.314 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.235 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 134.186α = 90
b = 35.777β = 131.08
c = 95.295γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations