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PDBsum entry 4m2r

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protein ligands metals links
Lyase/lyase inhibitor PDB id
4m2r
Jmol
Contents
Protein chain
257 a.a.
Ligands
BZ1
Metals
_ZN
Waters ×61
PDB id:
4m2r
Name: Lyase/lyase inhibitor
Title: Human carbonic anhydrase ii in complex with brinzolamide
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonate dehydratase ii, carbonic anhydrasE C, ca carbonic anhydrase ii, ca-ii. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.99Å     R-factor:   0.174     R-free:   0.216
Authors: M.P.Pinard,C.D.Boone,B.D.Rife,C.T.Supuran,R.Mckenna
Key ref: M.A.Pinard et al. (2013). Structural study of interaction between brinzolamide and dorzolamide inhibition of human carbonic anhydrases. Bioorg Med Chem, 21, 7210-7215. PubMed id: 24090602 DOI: 10.1016/j.bmc.2013.08.033
Date:
05-Aug-13     Release date:   06-Nov-13    
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: 10.1016/j.bmc.2013.08.033 Bioorg Med Chem 21:7210-7215 (2013)
PubMed id: 24090602  
 
 
Structural study of interaction between brinzolamide and dorzolamide inhibition of human carbonic anhydrases.
M.A.Pinard, C.D.Boone, B.D.Rife, C.T.Supuran, R.McKenna.
 
  ABSTRACT  
 
Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes that catalyze the reversible hydration of carbon dioxide and bicarbonate. Their pivotal role in metabolism, ubiquitous nature, and multiple isoforms (CA I-XIV) has made CAs an attractive drug target in clinical applications. The usefulness of CA inhibitors (CAIs) in the treatment of glaucoma and epilepsy are well documented. In addition several isoforms of CAs (namely, CA IX) also serve as biological markers for certain tumors, and therefore they have the potential for useful applications in the treatment of cancer. This is a structural study on the binding interactions of the widely used CA inhibitory drugs brinzolamide (marketed as AzoptĀ®) and dorzolamide (marketed as TrusoptĀ®) with CA II and a CA IX-mimic, which was created via site-directed mutagenesis of CA II cDNA such that the active site resembles that of CA IX. Also the inhibition of CA II and CA IX and molecular docking reveal brinzolamide to be a more potent inhibitor among the other catalytically active CA isoforms compared to dorzolamide. The structures show that the tail end of the sulfonamide inhibitor is critical in forming stabilizing interactions that influence tight binding; therefore, for future drug design it is the tail moiety that will ultimately determine isoform specificity.