1EOU

CRYSTAL STRUCTURE OF HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH AN ANTICONVULSANT SUGAR SULFAMATE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Crystal structure of human carbonic anhydrase II complexed with an anti-convulsant sugar sulphamate.

Recacha, R.Costanzo, M.J.Maryanoff, B.E.Chattopadhyay, D.

(2002) Biochem J 361: 437-441

  • DOI: https://doi.org/10.1042/0264-6021:3610437
  • Primary Citation of Related Structures:  
    1EOU

  • PubMed Abstract: 

    The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the widely used anti-epileptic drug topiramate, possesses anti-convulsant and carbonic anhydrase-inhibitory activities. We have studied the binding interactions of RWJ-37497 in the active site of human carbonic anhydrase II by X-ray crystallography. The atomic positions of the enzyme inhibitor complex were refined at a resolution of 2.1 A (1 A=0.1 nm) to the final crystallographic R and R(free) values of 0.18 and 0.23, respectively. The inhibitor co-ordinates to the active-site zinc ion through its oxygen atom and the ionized nitrogen atom of the sulphamate group by replacing the metal-bound water molecules, although the sulphamoyl oxygen atom provides a rather lengthy co-ordination. The 4,5-cyclic sulphate group is positioned in a hydrophobic pocket of the active site, making contacts with the residues Phe-131, Leu-198, Pro-201 and Pro-202. Since the ligand was found to be intact, concerns about RWJ-37947 irreversibly alkylating the enzyme through its 4,5-cyclic sulphate group were dispelled.


  • Organizational Affiliation

    Center for Biophysical Sciences and Engineering, and School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CARBONIC ANHYDRASE II (CA II)260Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SMS
Query on SMS

Download Ideal Coordinates CCD File 
C [auth A]SULFAMIC ACID 2,3-O-(1-METHYLETHYLIDENE)-4,5-O-SULFONYL-BETA-FRUCTOPYRANOSE ESTER
C9 H15 N O10 S2
GGOAQSGCBDRTHT-JAKMQLQISA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SMS BindingDB:  1EOU Ki: min: 12, max: 910 (nM) from 5 assay(s)
Kd: 10 (nM) from 1 assay(s)
IC50: 36 (nM) from 1 assay(s)
Binding MOAD:  1EOU IC50: 36 (nM) from 1 assay(s)
PDBBind:  1EOU IC50: 36 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.176 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.275α = 90
b = 41.39β = 104.11
c = 72.509γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-02-13
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-03-07
    Changes: Data collection
  • Version 1.4: 2024-02-07
    Changes: Data collection, Database references, Derived calculations
  • Version 1.5: 2024-03-13
    Changes: Source and taxonomy, Structure summary