3NB5

Human carbonic anhydrase II in complex with 2-(3-chloro-4-hydroxyphenyl)-N-(4-sulfamoylphenethyl)acetamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Natural Product-Based Phenols as Novel Probes for Mycobacterial and Fungal Carbonic Anhydrases

Davis, R.A.Hofmann, A.Osman, A.Hall, R.A.Muhlschlegel, F.A.Vullo, D.Innocenti, A.Supuran, C.T.Poulsen, S.A.

(2011) J Med Chem 54: 1682-1692

  • DOI: https://doi.org/10.1021/jm1013242
  • Primary Citation of Related Structures:  
    3NB5, 3P4V

  • PubMed Abstract: 

    In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as α-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal β-CAs, with the two best performing compounds displaying submicromolar inhibition with a preference for fungal over human CA inhibition of more than 2 orders of magnitude. These compounds provide the first example of non-sulfonamide inhibitors that display β over α CA enzyme selectivity. Structural characterization of the library compounds in complex with human CA II revealed a novel binding mode whereby a methyl ester interacts via a water molecule with the active site zinc.


  • Organizational Affiliation

    Eskitis Institute, Griffith University, Nathan, Queensland 4111, 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: carbonic anhydrase ii
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
R21 PDBBind:  3NB5 Ki: 18 (nM) from 1 assay(s)
BindingDB:  3NB5 Ki: 18 (nM) from 1 assay(s)
Binding MOAD:  3NB5 Ki: 18 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.207 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.67α = 90
b = 41.54β = 104.89
c = 72.47γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
CNSrefinement
MOSFLMdata reduction
SCALAdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description