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PDBsum entry 3kwa

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protein ligands metals links
Lyase PDB id
3kwa
Jmol
Contents
Protein chain
256 a.a. *
Ligands
SPM
Metals
_ZN
_HG
Waters ×180
* Residue conservation analysis
PDB id:
3kwa
Name: Lyase
Title: Polyamines inhibit carbonic anhydrases
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratas carbonic anhydrasE C, cac. Ec: 4.2.1.1
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: the protein was purchased from sigma-aldrich
Resolution:
2.00Å     R-factor:   0.236     R-free:   0.286
Authors: C.Temperini
Key ref: F.Carta et al. (2010). Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem, 53, 5511-5522. PubMed id: 20590092 DOI: 10.1021/jm1003667
Date:
01-Dec-09     Release date:   14-Jul-10    
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: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   10 terms 
  Biological process     angiotensin-mediated signaling pathway   20 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/jm1003667 J Med Chem 53:5511-5522 (2010)
PubMed id: 20590092  
 
 
Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule.
F.Carta, C.Temperini, A.Innocenti, A.Scozzafava, K.Kaila, C.T.Supuran.
 
  ABSTRACT  
 
Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, phenols, and coumarins. Polyamines such as spermine, spermidine, and many synthetic congeners are described to constitute a novel class of CA inhibitors (CAIs), interacting with the different CA isozymes with efficiency from the low nanomolar to millimolar range. The main structure-activity relationship for these CAIs have been delineated: the length of the molecule, number of amine moieties, and their functionalization are the main parameters controlling activity. The X-ray crystal structure of the CA II-spermine adduct allowed understanding of the inhibition mechanism. Spermine anchors to the nonprotein zinc ligand through a network of hydrogen bonds. Its distal amine moiety makes hydrogen bonds with residues Thr200 and Pro201, which further stabilize the adduct. Spermine binds differently compared to sulfonamides, phenols, or coumarins, rendering possible to develop CAIs with a diverse inhibition mechanism, profile, and selectivity for various isoforms.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21549597 F.Mincione, F.Benedini, S.Biondi, A.Cecchi, C.Temperini, G.Formicola, I.Pacileo, A.Scozzafava, E.Masini, and C.T.Supuran (2011).
Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action.
  Bioorg Med Chem Lett, 21, 3216-3221.
PDB code: 3ni5
20922253 F.Pacchiano, M.Aggarwal, B.S.Avvaru, A.H.Robbins, A.Scozzafava, R.McKenna, and C.T.Supuran (2010).
Selective hydrophobic pocket binding observed within the carbonic anhydrase II active site accommodate different 4-substituted-ureido-benzenesulfonamides and correlate to inhibitor potency.
  Chem Commun (Camb), 46, 8371-8373.
PDB codes: 3mzc 3n0n 3n2p 3n3j 3n4b
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