4Q78

Structure-assisted design of carborane-based inhibitors of carbonic anhydrase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Carborane-based carbonic anhydrase inhibitors: insight into CAII/CAIX specificity from a high-resolution crystal structure, modeling, and quantum chemical calculations.

Mader, P.Pecina, A.Cigler, P.Lepsik, M.Sicha, V.Hobza, P.Gruner, B.Fanfrlik, J.Brynda, J.Rezacova, P.

(2014) Biomed Res Int 2014: 389869-389869

  • DOI: https://doi.org/10.1155/2014/389869
  • Primary Citation of Related Structures:  
    4Q78

  • PubMed Abstract: 

    Carborane-based compounds are promising lead structures for development of inhibitors of carbonic anhydrases (CAs). Here, we report structural and computational analysis applicable to structure-based design of carborane compounds with selectivity toward the cancer-specific CAIX isoenzyme. We determined the crystal structure of CAII in complex with 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane at 1.0 Å resolution and used this structure to model the 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane interactions with CAIX. A virtual glycine scan revealed the contributions of individual residues to the energy of binding of 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane to CAII and CAIX, respectively.


  • Organizational Affiliation

    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 140 00 Prague 4, Czech Republic ; Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada M5G 1L7.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2258Homo sapiensMutation(s): 0 
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.00 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.2α = 90
b = 41.725β = 104.36
c = 72.155γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-18
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Advisory, Data collection, Database references, Derived calculations