3HKT

Human carbonic anhydrase II in complex with alpha-D-Glucopyranosyl-(1->4)-1-thio-beta-D-glucopyranosylsulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.36 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.155 
  • R-Value Observed: 0.159 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases.

Lopez, M.Paul, B.Hofmann, A.Morizzi, J.Wu, Q.K.Charman, S.A.Innocenti, A.Vullo, D.Supuran, C.T.Poulsen, S.A.

(2009) J Med Chem 52: 6421-6432

  • DOI: https://doi.org/10.1021/jm900914e
  • Primary Citation of Related Structures:  
    3HKN, 3HKQ, 3HKT, 3HKU

  • PubMed Abstract: 

    In this paper, we present a new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1-10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with K(i)s in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand-protein interactions of these novel carbohydrate-based sulfonamides with CA.


  • Organizational Affiliation

    Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Queensland 4111, Australia.


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
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
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-galactopyranose-(1-4)-(1S)-1,5-anhydro-1-sulfamoyl-D-galactitol
B
2N/AN/A
Glycosylation Resources
GlyTouCan:  G46053DQ
GlyCosmos:  G46053DQ
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

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

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.36 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.155 
  • R-Value Observed: 0.159 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.347α = 90
b = 41.671β = 104.92
c = 72.488γ = 90
Software Package:
Software NamePurpose
StructureStudiodata collection
AMoREphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-10-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2019-12-25
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Non-polymer description, Structure summary