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PDBsum entry 3hlj

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protein ligands metals links
Lyase PDB id
3hlj
Jmol
Contents
Protein chain
257 a.a. *
Ligands
V21
UNX-UNX-UNX-UNX-
UNX-UNX-UNX-UNX
Metals
_ZN
_NA
Waters ×219
* Residue conservation analysis
PDB id:
3hlj
Name: Lyase
Title: Crystal structure of human carbonic anhydrase isozyme ii wit methylthiobenzimidazo[1,2-c][1,2,3]thiadiazol-7-sulfonamide
Structure: Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, ca-ii, carbonate dehydratas carbonic anhydrasE C, cac. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ca2. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.44Å     R-factor:   0.178     R-free:   0.206
Authors: S.Grazulis,E.Manakova,D.Golovenko
Key ref: L.Baranauskienė et al. (2010). Inhibition and binding studies of carbonic anhydrase isozymes I, II and IX with benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides. J Enzyme Inhib Med Chem, 25, 863-870. PubMed id: 20166809 DOI: 10.3109/14756360903571685
Date:
27-May-09     Release date:   02-Mar-10    
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: 10.3109/14756360903571685 J Enzyme Inhib Med Chem 25:863-870 (2010)
PubMed id: 20166809  
 
 
Inhibition and binding studies of carbonic anhydrase isozymes I, II and IX with benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides.
L.Baranauskienė, M.Hilvo, J.Matulienė, D.Golovenko, E.Manakova, V.Dudutienė, V.Michailovienė, J.Torresan, J.Jachno, S.Parkkila, A.Maresca, C.T.Supuran, S.Gražulis, D.Matulis.
 
  ABSTRACT  
 
The binding and inhibition strength of a series of benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides were determined for recombinant human carbonic anhydrase isoforms I, II, and IX. The inhibition strength was determined by a stop-flow method to measure carbon dioxide hydration. Inhibitor-enzyme binding was determined by two biophysical techniques - isothermal titration calorimetry and thermal shift assay. The co-crystal structure was determined by X-ray crystallography. Comparing the results obtained using three different inhibition and binding methods increased the accuracy of compound affinity ranking and the ability to determine compound inhibitory specificity towards a particular carbonic anhydrase isoform. In most cases, all three methods yielded the same results despite using very different approaches to measure the binding and inhibition reactions. Some of the compounds studied are submicromolar inhibitors of the isoform IX, a prominent cancer target.
 

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
21345327 Z.Toleikis, P.Cimmperman, V.Petrauskas, and D.Matulis (2011).
Determination of the volume changes induced by ligand binding to heat shock protein 90 using high-pressure denaturation.
  Anal Biochem, 413, 171-178.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.