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PDBsum entry 3dd8

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protein ligands metals links
Lyase PDB id
3dd8
Jmol
Contents
Protein chain
256 a.a. *
Ligands
2C7
Metals
_ZN
_HG
Waters ×147
* Residue conservation analysis
PDB id:
3dd8
Name: Lyase
Title: Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate emd-486019 with twelve mammalian isoforms: kinetic and x-ray crystallographic studies
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C, cac. Engineered: yes
Source: Synthetic: yes. Other_details: chemically synthesized. This sequence occurs naturally in humans(homo sapiens).
Resolution:
1.90Å     R-factor:   0.208     R-free:   0.256
Authors: C.Temperini,A.Innocenti,A.Scozzafava,C.T.Supuran
Key ref: C.Temperini et al. (2008). Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-ray crystallographic studies. Bioorg Med Chem Lett, 18, 4282-4286. PubMed id: 18640037 DOI: 10.1016/j.bmcl.2008.06.105
Date:
05-Jun-08     Release date:   12-Aug-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00918  (CAH2_HUMAN) -  Carbonic anhydrase 2
Seq:
Struc:
260 a.a.
256 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: 10.1016/j.bmcl.2008.06.105 Bioorg Med Chem Lett 18:4282-4286 (2008)
PubMed id: 18640037  
 
 
Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-ray crystallographic studies.
C.Temperini, A.Innocenti, A.Scozzafava, C.T.Supuran.
 
  ABSTRACT  
 
The new antitumor sulfamate EMD 486019 was investigated for its interaction with twelve catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isozymes, hCA I - XIV. Similarly to 667-Coumate, a structurally related compound in phase II clinical trials as steroid sulfatase/CA inhibitor with potent antitumor properties, EMD 486019 acts as a strong inhibitor of isozymes CA II, VB, VII, IX, XII, and XIV (K(I)s in the range of 13-19nM) being less effective against other isozymes (K(I)s in the range of 66-3600nM against hCA I, IV, VA, VI, and mCA XIII, respectively). The complete inhibition profile of 667-Coumate against these mammalian CAs is also reported here for the first time. Comparing the X-ray crystal structures of the two adducts of CA II with EMD 486019 and 667-Coumate, distinct orientations of the bound sulfamates within the enzyme cavity were observed, which account for their distinct inhibition profiles. CA II/IX potent inhibitors belonging to the sulfamate class are thus valuable clinical candidates with potential for development as antitumor agents with a multifactorial mechanism of action.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20976313 W.J.Spillane, S.Thea, G.Cevasco, M.J.Hynes, C.J.McCaw, and N.P.Maguire (2011).
Mechanisms of hydrolysis of phenyl- and benzyl 4-nitrophenyl-sulfamate esters.
  Org Biomol Chem, 9, 523-530.  
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