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PDBsum entry 3p5a

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protein ligands metals links
Lyase/inhibitor PDB id
3p5a
Jmol
Contents
Protein chain
257 a.a.
Ligands
IT2
DMS
Metals
_ZN
Waters ×300
PDB id:
3p5a
Name: Lyase/inhibitor
Title: Human carbonic anhydrase complexed with sodium morpholinocarbodithioate
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: 469008.
Resolution:
1.49Å     R-factor:   0.149     R-free:   0.169
Authors: M.Aggarwal,R.Mckenna
Key ref: F.Carta et al. (2012). Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo. J Med Chem, 55, 1721-1730. PubMed id: 22276570 DOI: 10.1021/jm300031j
Date:
08-Oct-10     Release date:   19-Oct-11    
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/jm300031j J Med Chem 55:1721-1730 (2012)
PubMed id: 22276570  
 
 
Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo.
F.Carta, M.Aggarwal, A.Maresca, A.Scozzafava, R.McKenna, E.Masini, C.T.Supuran.
 
  ABSTRACT  
 
A series of dithiocarbamates were prepared by reaction of primary/secondary amines with carbon disulfide in the presence of bases. These compounds were tested for the inhibition of four human (h) isoforms of the zinc enzyme carbonic anhydrase, CA (EC 4.2.1.1), hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX). Several low nanomolar inhibitors targeting these CAs were detected. The X-ray crystal structure of the hCA II adduct with morpholine dithiocarbamate evidenced the inhibition mechanism of these compounds, which coordinate to the metal ion through a sulfur atom from the dithiocarbamate zinc-binding function. Some dithiocarbamates showed an effective intraocular pressure lowering activity in an animal model of glucoma.