1OKL

CARBONIC ANHYDRASE II COMPLEX WITH THE 1OKL INHIBITOR 5-DIMETHYLAMINO-NAPHTHALENE-1-SULFONAMIDE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.185 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Unexpected binding mode of the sulfonamide fluorophore 5-dimethylamino-1-naphthalene sulfonamide to human carbonic anhydrase II. Implications for the development of a zinc biosensor.

Nair, S.K.Elbaum, D.Christianson, D.W.

(1996) J Biol Chem 271: 1003-1007

  • DOI: https://doi.org/10.1074/jbc.271.2.1003
  • Primary Citation of Related Structures:  
    1OKL

  • PubMed Abstract: 

    The three-dimensional structure of human carbonic anhydrase II (CAII) complexed with the sulfonamide fluorophore 5-dimethylamino-1-naphthalene sulfonamide (dansylamide) has been determined to 2.1-A resolution by x-ray crystallographic methods. Unlike other arylsulfonamide inhibitors of CAII, the naphthyl ring of dansylamide binds in a hydrophobic pocket in the active site, making van der Waals contacts with Val-121, Phe-131, Val-143, Leu-198, and Trp-209. Interestingly, a conformational change of Leu-198 is required to accommodate dansylamide binding, which rationalizes the enhanced dansylamide affinity measured for certain Leu-198 variants (Nair, S. K., Krebs, J.F., Christianson, D. W., and Fierke, C. A. (1995) Biochemistry 34, 3981-3989). Modeling studies indicate that a second binding mode, in which the fused aromatic ring is rotated out of the hydrophobic pocket, is sterically feasible. Both experimentally observed and modeled binding modes have implications for new leads in the design of avid CAII inhibitors. Finally, the structure of the CAII-dansylamide complex has implications for its exploitation in zinc biosensor applications, and possible routes toward the optimization of fluorophore design are considered on the basis on this structure.


  • Organizational Affiliation

    Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CARBONIC ANHYDRASE II259Homo 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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MNS
Query on MNS

Download Ideal Coordinates CCD File 
D [auth A]5-(DIMETHYLAMINO)-1-NAPHTHALENESULFONAMIDE
C12 H14 N2 O2 S
TYNBFJJKZPTRKS-UHFFFAOYSA-N
HG
Query on HG

Download Ideal Coordinates CCD File 
B [auth A]MERCURY (II) ION
Hg
BQPIGGFYSBELGY-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
MNS Binding MOAD:  1OKL Kd: 930 (nM) from 1 assay(s)
PDBBind:  1OKL Kd: 930 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.185 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.7α = 90
b = 41.7β = 104.6
c = 73γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
MOSFLMdata reduction
CCP4data scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-01-11
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations, Other