5EH8

human carbonic anhydrase II in complex with ligand


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.38 Å
  • R-Value Free: 0.173 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.151 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination.

Woods, L.A.Dolezal, O.Ren, B.Ryan, J.H.Peat, T.S.Poulsen, S.A.

(2016) J Med Chem 59: 2192-2204

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01940
  • Primary Citation of Related Structures:  
    5EH5, 5EH7, 5EH8, 5EHV, 5EHW, 5FLO, 5FLP, 5FLQ, 5FLR, 5FLS, 5FLT, 5FNG, 5FNH, 5FNI, 5FNJ, 5FNK, 5FNL, 5FNM

  • PubMed Abstract: 

    Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.


  • Organizational Affiliation

    Griffith University , Eskitis Institute for Drug Discovery, Brisbane, Queensland Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens)
Explore P00918 
Go to UniProtKB:  P00918
PHAROS:  P00918
GTEx:  ENSG00000104267 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00918
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
5O6 Binding MOAD:  5EH8 Kd: 7.91e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.38 Å
  • R-Value Free: 0.173 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.151 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.023α = 90
b = 41.424β = 104.21
c = 72.039γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2016-03-09 
  • Deposition Author(s): Ren, B.

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-09
    Type: Initial release
  • Version 1.1: 2016-03-23
    Changes: Database references
  • Version 1.2: 2024-03-06
    Changes: Data collection, Database references, Derived calculations