2FOV

Human Carbonic Anhydrase II complexed with two-prong inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.15 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.143 

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This is version 1.3 of the entry. See complete history


Literature

Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with two-prong inhibitors reveal the molecular basis of high affinity.

Jude, K.M.Banerjee, A.L.Haldar, M.K.Manokaran, S.Roy, B.Mallik, S.Srivastava, D.K.Christianson, D.W.

(2006) J Am Chem Soc 128: 3011-3018

  • DOI: https://doi.org/10.1021/ja057257n
  • Primary Citation of Related Structures:  
    2FOQ, 2FOS, 2FOU, 2FOV, 2FOY

  • PubMed Abstract: 

    The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors are reported. Each inhibitor contains a benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu(2+)) prong separated by linkers of different lengths and compositions. The ionized NH(-) group of each benzenesulfonamide coordinates to the active site Zn(2+) ion; the IDA-Cu(2+) prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII and H200 of CAI. This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases.


  • Organizational Affiliation

    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic Anhydrase II260Homo sapiensMutation(s): 1 
Gene Names: CA2
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
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CMH
Query on CMH
A
L-PEPTIDE LINKINGC4 H9 Hg N O2 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
B30 Binding MOAD:  2FOV Kd: 28 (nM) from 1 assay(s)
PDBBind:  2FOV Kd: 28 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.15 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.143 
  • R-Value Observed: 0.143 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.362α = 90
b = 41.482β = 104.34
c = 72.234γ = 90
Software Package:
Software NamePurpose
SHELXmodel building
SHELXL-97refinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-04-04
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description