4Y4D

Endothiapepsin in complex with fragment B51


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.27 Å
  • R-Value Free: 0.145 
  • R-Value Work: 0.117 
  • R-Value Observed: 0.119 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

Huschmann, F.U.Linnik, J.Sparta, K.Uhlein, M.Wang, X.Metz, A.Schiebel, J.Heine, A.Klebe, G.Weiss, M.S.Mueller, U.

(2016) Acta Crystallogr F Struct Biol Commun 72: 346-355

  • DOI: https://doi.org/10.1107/S2053230X16004623
  • Primary Citation of Related Structures:  
    4Y38, 4Y3J, 4Y3Y, 4Y48, 4Y4D, 4Y4G, 4Y4J, 4ZE6, 4ZEA

  • PubMed Abstract: 

    Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.


  • Organizational Affiliation

    Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Albert-Einstein-Strasse 15, D-12489 Berlin, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endothiapepsin330Cryphonectria parasiticaMutation(s): 0 
EC: 3.4.23.22
UniProt
Find proteins for P11838 (Cryphonectria parasitica)
Explore P11838 
Go to UniProtKB:  P11838
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11838
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CFF
Query on CFF

Download Ideal Coordinates CCD File 
L [auth A]CAFFEINE
C8 H10 N4 O2
RYYVLZVUVIJVGH-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A],
D [auth A],
E [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A],
J [auth A],
K [auth A]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A]
ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.27 Å
  • R-Value Free: 0.145 
  • R-Value Work: 0.117 
  • R-Value Observed: 0.119 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.3α = 90
b = 72.936β = 109.14
c = 52.508γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Cootmodel building
XDSdata reduction
XDSdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
BMBFGermany05K13RM1

Revision History  (Full details and data files)

  • Version 1.0: 2016-02-17
    Type: Initial release
  • Version 1.1: 2016-05-04
    Changes: Database references
  • Version 1.2: 2016-05-11
    Changes: Database references