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PDBsum entry 3hkn

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protein ligands metals links
Lyase PDB id
3hkn
Jmol
Contents
Protein chain
257 a.a. *
Ligands
MFS
GOL ×2
Metals
_ZN
Waters ×92
* Residue conservation analysis
PDB id:
3hkn
Name: Lyase
Title: Human carbonic anhydrase ii in complex with (2,3,4,6-tetra-o beta-d-galactopyranosyl) -(1-4)-1,2,3,6-tetra-o-acetyl-1-th glucopyranosylsulfonamide
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratas carbonic anhydrasE C, cac. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2, carbonic anhydrase ii. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.198     R-free:   0.220
Authors: B.Paul,S.-A.Poulsen,A.Hofmann
Key ref: M.Lopez et al. (2009). S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases. J Med Chem, 52, 6421-6432. PubMed id: 19827837 DOI: 10.1021/jm900914e
Date:
25-May-09     Release date:   13-Oct-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
257 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.1  - Carbonate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
H(2)CO(3)
= CO(2)
+ H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   11 terms 
  Biological process     angiotensin-mediated signaling pathway   21 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/jm900914e J Med Chem 52:6421-6432 (2009)
PubMed id: 19827837  
 
 
S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases.
M.Lopez, B.Paul, A.Hofmann, J.Morizzi, Q.K.Wu, S.A.Charman, A.Innocenti, D.Vullo, C.T.Supuran, S.A.Poulsen.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20505865 V.Alterio, S.M.Monti, E.Truppo, C.Pedone, C.T.Supuran, and G.De Simone (2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.
  Org Biomol Chem, 8, 3528-3533.
PDB code: 3lxe
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