 |
PDBsum entry 5fdc
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Lyase
|
|
|
Title:
|
|
Crystal structure of human carbonic anhydrase ii in complex with the anticonvulsant sulfamide jnj-26990990 and its s,s-dioxide analog.
|
|
Structure:
|
|
Carbonic anhydrase 2. Chain: a. Synonym: carbonate dehydratase ii,carbonic anhydrasE C,cac,carbonic anhydrase ii,ca-ii. Ec: 4.2.1.1
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606
|
|
Resolution:
|
|
|
1.75Å
|
R-factor:
|
0.170
|
R-free:
|
0.204
|
|
|
Authors:
|
|
A.Di Fiore,G.De Simone,V.Alterio,V.Riccio,J.-Y.Winum,F.Carta, C.T.Supuran
|
|
Key ref:
|
|
A.Di Fiore
et al.
(2016).
The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies.
Org Biomol Chem,
14,
4853-4858.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
16-Dec-15
|
Release date:
|
18-May-16
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P00918
(CAH2_HUMAN) -
Carbonic anhydrase 2 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
260 a.a.
258 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class 2:
|
|
E.C.4.2.1.1
- carbonic anhydrase.
|
|
|
|
|
|
|
Reaction:
|
|
hydrogencarbonate + H+ = CO2 + H2O
|
|
|
|
|
|
hydrogencarbonate
|
+
|
H(+)
|
=
|
CO2
|
+
|
H2O
|
|
|
|
|
|
|
|
|
|
Cofactor:
|
|
Zn(2+)
|
|
|
|
|
|
Enzyme class 3:
|
|
E.C.4.2.1.69
- cyanamide hydratase.
|
|
|
|
|
|
|
Reaction:
|
|
urea = cyanamide + H2O
|
|
|
|
|
|
urea
|
=
|
cyanamide
|
+
|
H2O
|
|
|
|
|
|
|
|
|
|
|
|
|
Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
Org Biomol Chem
14:4853-4858
(2016)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies.
|
|
A.Di Fiore,
G.De Simone,
V.Alterio,
V.Riccio,
J.Y.Winum,
F.Carta,
C.T.Supuran.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
JNJ-26990990 ((benzo[b]thien-3-yl)methyl)sulfamide, a sulfamide derivative
structurally related to the antiepileptic drug zonisamide, was reported to be
devoid of carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties. Here we
report that JNJ-26990990 and its S,S-dioxide analog significantly inhibit six
human (h) isoforms, hCA I, II, VII, IX, XII and XIV, involved in crucial
physiological processes. Inhibition and X-ray crystallographic data for the
binding of the two compounds to these enzymes show significant similarity with
the zonisamide inhibitory pattern. These findings prompted us to reconsider the
structural/pharmacological requirements for designing effective antiepileptics
possessing zinc-binding groups of the sulfamide, sulfamate or sulfonamide type
in their molecules.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
