PDBsum entry 3daz

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Lyase PDB id
Jmol PyMol
Protein chain
257 a.a. *
Waters ×182
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Use of carbonic anhydrase ii, ix active-site mimic, for the screening inhibitors for possible anti-cancer properties
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, c carbonic anhydrasE C, cac. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.60Å     R-factor:   0.163     R-free:   0.190
Authors: C.Genis,K.H.Sippel,N.Case,L.Govindasamy,M.Agbandje-Mckenna,R
Key ref: C.Genis et al. (2009). Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties. Biochemistry, 48, 1322-1331. PubMed id: 19170619
30-May-08     Release date:   03-Mar-09    
Go to PROCHECK summary

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

 Enzyme reactions 
   Enzyme class: E.C.  - Carbonic anhydrase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: H2CO3 = CO2 + H2O
= 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   22 terms 
  Biochemical function     protein binding     6 terms  


    Added reference    
Biochemistry 48:1322-1331 (2009)
PubMed id: 19170619  
Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.
C.Genis, K.H.Sippel, N.Case, W.Cao, B.S.Avvaru, L.J.Tartaglia, L.Govindasamy, C.Tu, M.Agbandje-McKenna, D.N.Silverman, C.J.Rosser, R.McKenna.
Recently, a convincing body of evidence has accumulated suggesting that the overexpression of carbonic anhydrase isozyme IX (CA IX) in some cancers contributes to the acidification of the extracellular matrix, which in turn promotes the growth and metastasis of the tumor. These observations have made CA IX an attractive drug target for the selective treatment of certain cancers. Currently, there is no available X-ray crystal structure of CA IX, and this lack of availability has hampered the rational design of selective CA IX inhibitors. In light of these observations and on the basis of structural alignment homology, using the crystal structure of carbonic anhydrase II (CA II) and the sequence of CA IX, a double mutant of CA II with Ala65 replaced by Ser and Asn67 replaced by Gln has been constructed to resemble the active site of CA IX. This CA IX mimic has been characterized kinetically using (18)O-exchange and structurally using X-ray crystallography, alone and in complex with five CA sulfonamide-based inhibitors (acetazolamide, benzolamide, chlorzolamide, ethoxzolamide, and methazolamide), and compared to CA II. This structural information has been evaluated by both inhibition studies and in vitro cytotoxicity assays and shows a correlated structure-activity relationship. Kinetic and structural studies of CA II and CA IX mimic reveal chlorzolamide to be a more potent inhibitor of CA IX, inducing an active-site conformational change upon binding. Additionally, chlorzolamide appears to be cytotoxic to prostate cancer cells. This preliminary study demonstrates that the CA IX mimic may provide a useful model to design more isozyme-specific CA IX inhibitors, which may lead to development of new therapeutic treatments of some cancers.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21244635 A.Stander, F.Joubert, and A.Joubert (2011).
Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs.
  Chem Biol Drug Des, 77, 173-181.  
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