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PDBsum entry 4kni

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protein ligands metals links
Lyase/lyase inhibitor PDB id
4kni
Jmol
Contents
Protein chain
257 a.a.
Ligands
DMS ×2
MES
E1E
Metals
_ZN
Waters ×190
PDB id:
4kni
Name: Lyase/lyase inhibitor
Title: Crystal structure of human carbonic anhydrase isozyme ii wit chloro-4-{[(4,6-dimethylpyrimidin-2-yl) sulfanyl]acetyl}benzenesulfonamide
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:
1.80Å     R-factor:   0.169     R-free:   0.225
Authors: A.Smirnov,E.Manakova,S.Grazulis
Key ref: E.Čapkauskaitė et al. (2013). Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII. Bioorg Med Chem, 21, 6937-6947. PubMed id: 24103428 DOI: 10.1016/j.bmc.2013.09.029
Date:
10-May-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   22 terms 
  Biochemical function     protein binding     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmc.2013.09.029 Bioorg Med Chem 21:6937-6947 (2013)
PubMed id: 24103428  
 
 
Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII.
E.Čapkauskaitė, A.Zubrienė, A.Smirnov, J.Torresan, M.Kišonaitė, J.Kazokaitė, J.Gylytė, V.Michailovienė, V.Jogaitė, E.Manakova, S.Gražulis, S.Tumkevičius, D.Matulis.
 
  ABSTRACT  
 
Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms.