4DD8

ADAM-8 metalloproteinase domain with bound batimastat


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.192 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure of human ADAM-8 catalytic domain complexed with batimastat.

Hall, T.Shieh, H.S.Day, J.E.Caspers, N.Chrencik, J.E.Williams, J.M.Pegg, L.E.Pauley, A.M.Moon, A.F.Krahn, J.M.Fischer, D.H.Kiefer, J.R.Tomasselli, A.G.Zack, M.D.

(2012) Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 616-621

  • DOI: https://doi.org/10.1107/S1744309112015618
  • Primary Citation of Related Structures:  
    4DD8

  • PubMed Abstract: 

    The role of ADAM-8 in cancer and inflammatory diseases such as allergy, arthritis and asthma makes it an attractive target for drug development. Therefore, the catalytic domain of human ADAM-8 was expressed, purified and crystallized in complex with a hydroxamic acid inhibitor, batimastat. The crystal structure of the enzyme-inhibitor complex was refined to 2.1 Å resolution. ADAM-8 has an overall fold similar to those of other ADAM members, including a central five-stranded β-sheet and a catalytic Zn(2+) ion. However, unique differences within the S1' binding loop of ADAM-8 are observed which might be exploited to confer specificity and selectivity to ADAM-8 competitive inhibitors for the treatment of diseases involving this enzyme.


  • Organizational Affiliation

    Pfizer Inc, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Disintegrin and metalloproteinase domain-containing protein 8
A, B, C, D
208Homo sapiensMutation(s): 0 
Gene Names: ADAM8MS2
EC: 3.4.24
UniProt & NIH Common Fund Data Resources
Find proteins for P78325 (Homo sapiens)
Explore P78325 
Go to UniProtKB:  P78325
PHAROS:  P78325
GTEx:  ENSG00000151651 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP78325
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BAT
Query on BAT

Download Ideal Coordinates CCD File 
E [auth A],
M [auth B],
S [auth C],
Y [auth D]
4-(N-HYDROXYAMINO)-2R-ISOBUTYL-2S-(2-THIENYLTHIOMETHYL)SUCCINYL-L-PHENYLALANINE-N-METHYLAMIDE
C23 H31 N3 O4 S2
XFILPEOLDIKJHX-QYZOEREBSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
AA [auth D],
G [auth A],
O [auth B],
U [auth C]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
F [auth A],
N [auth B],
T [auth C],
Z [auth D]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
K [auth A],
L [auth A]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
CA [auth D],
I [auth A],
Q [auth B],
W [auth C]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
BA [auth D]
DA [auth D]
H [auth A]
J [auth A]
P [auth B]
BA [auth D],
DA [auth D],
H [auth A],
J [auth A],
P [auth B],
R [auth B],
V [auth C],
X [auth C]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.255 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.192 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.6α = 90
b = 50.9β = 102.4
c = 93.5γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
MOLREPphasing
PHENIXrefinement
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-06-06
    Type: Initial release
  • Version 1.1: 2012-06-27
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description