3LJZ

Crystal Structure of Human MMP-13 complexed with an Amino-2-indanol compound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure analysis reveals the flexibility of the ADAMTS-5 active site.

Shieh, H.S.Tomasselli, A.G.Mathis, K.J.Schnute, M.E.Woodard, S.S.Caspers, N.Williams, J.M.Kiefer, J.R.Munie, G.Wittwer, A.Malfait, A.M.Tortorella, M.D.

(2011) Protein Sci 20: 735-744

  • DOI: https://doi.org/10.1002/pro.606
  • Primary Citation of Related Structures:  
    3LJT, 3LJZ

  • PubMed Abstract: 

    A ((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl) succinamide derivative (here referred to as Compound 12) shows significant activity toward many matrix metalloproteinases (MMPs), including MMP-2, MMP-8, MMP-9, and MMP-13. Modeling studies had predicted that this compound would not bind to ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) due to its shallow S1' pocket. However, inhibition analysis revealed it to be a nanomolar inhibitor of both ADAMTS-4 and -5. The observed inconsistency was explained by analysis of crystallographic structures, which showed that Compound 12 in complex with the catalytic domain of ADAMTS-5 (cataTS5) exhibits an unusual conformation in the S1' pocket of the protein. This first demonstration that cataTS5 can undergo an induced conformational change in its active site pocket by a molecule like Compound 12 should enable the design of new aggrecanase inhibitors with better potency and selectivity profiles.


  • Organizational Affiliation

    Pfizer Global Research and Development, St. Louis, Missouri 63017, USA. shiehouse@sbcglobal.net


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Collagenase 3
A, B, C, D
164Homo sapiensMutation(s): 1 
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 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LA3
Query on LA3

Download Ideal Coordinates CCD File 
AA [auth C],
K [auth A],
KA [auth D],
S [auth B]
(2R)-2-[4-(1,3-benzodioxol-5-yl)benzyl]-N~4~-hydroxy-N~1~-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide
C27 H26 N2 O6
MJTVUROZTDIMFT-MZEQIWSPSA-N
EPE
Query on EPE

Download Ideal Coordinates CCD File 
FA [auth D],
GA [auth D],
P [auth B],
X [auth C]
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID
C8 H18 N2 O4 S
JKMHFZQWWAIEOD-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
HA [auth D]
I [auth A]
IA [auth D]
J [auth A]
JA [auth D]
HA [auth D],
I [auth A],
IA [auth D],
J [auth A],
JA [auth D],
Q [auth B],
R [auth B],
Y [auth C],
Z [auth C]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN
Query on ZN

Download Ideal Coordinates CCD File 
DA [auth D]
EA [auth D]
G [auth A]
H [auth A]
N [auth B]
DA [auth D],
EA [auth D],
G [auth A],
H [auth A],
N [auth B],
O [auth B],
V [auth C],
W [auth C]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
BA [auth D]
CA [auth D]
E [auth A]
F [auth A]
L [auth B]
BA [auth D],
CA [auth D],
E [auth A],
F [auth A],
L [auth B],
M [auth B],
T [auth C],
U [auth C]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LA3 PDBBind:  3LJZ Ki: 7.3 (nM) from 1 assay(s)
Binding MOAD:  3LJZ Ki: 7.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.604α = 90
b = 94.927β = 90
c = 120.406γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations