8DJ9

Carbonic Anhydrase II in complex with Ibuprofen


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.169 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.144 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Ibuprofen: a weak inhibitor of carbonic anhydrase II.

Combs, J.Andring, J.McKenna, R.

(2022) Acta Crystallogr F Struct Biol Commun 78: 395-402

  • DOI: https://doi.org/10.1107/S2053230X22009761
  • Primary Citation of Related Structures:  
    8DJ9

  • PubMed Abstract: 

    Carbonic anhydrases (CAs) are drug targets for a variety of diseases. While many clinically relevant CA inhibitors are sulfonamide-based, novel CA inhibitors are being developed that incorporate alternative zinc-binding groups, such as carboxylic acid moieties, to develop CA isoform-specific inhibitors. Here, the X-ray crystal structure of human CA II (hCA II) in complex with the carboxylic acid ibuprofen [2-(4-isobutylphenyl)propanoic acid, a common over-the-counter nonsteroidal anti-inflammatory drug] is reported to 1.54 Å resolution. The binding of ibuprofen is overlaid with the structures of other carboxylic acids in complex with hCA II to compare their inhibition mechanisms by direct or indirect (via a water) binding to the active-site zinc. Additionally, enzyme-inhibition assays using ibuprofen, nicotinic acid and ferulic acid were performed with hCA II to determine their IC 50 values and were compared with those of other carboxylic acid binders. This study discusses the potential development of CA inhibitors utilizing the carboxylic acid moiety.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.


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 (PDB Primary Data), 4.2.1.69 (UniProt)
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
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IZP (Subject of Investigation/LOI)
Query on IZP

Download Ideal Coordinates CCD File 
D [auth A](2R)-2-[4-(2-methylpropyl)phenyl]propanoic acid
C13 H18 O2
HEFNNWSXXWATRW-SNVBAGLBSA-N
TRS
Query on TRS

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A]
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
GOL
Query on GOL

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

Download Ideal Coordinates CCD File 
G [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.169 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.144 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.69α = 90
b = 41.711β = 104.21
c = 72.287γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Not funded--

Revision History  (Full details and data files)

  • Version 1.0: 2022-11-09
    Type: Initial release
  • Version 1.1: 2023-10-18
    Changes: Data collection, Refinement description
  • Version 1.2: 2024-05-01
    Changes: Database references