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PDBsum entry 3b4f
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Contents |
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* Residue conservation analysis
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PDB id:
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Lyase
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Title:
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Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3- phenyl-1h-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and x-ray crystallographic studies
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Structure:
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Carbonic anhydrase 2. Chain: a. Synonym: carbonic anhydrase ii, carbonate dehydratase ii, ca-ii, carbonic anhydrasE C. Ec: 4.2.1.1
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Source:
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Homo sapiens. Human. Organism_taxid: 9606
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Resolution:
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1.89Å
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R-factor:
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0.198
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R-free:
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0.239
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Authors:
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O.Guzel,C.Temperini,A.Innocenti,A.Scozzafava,A.Salman,C.T.Supuran
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Key ref:
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O.Güzel
et al.
(2008).
Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.
Bioorg Med Chem Lett,
18,
152-158.
PubMed id:
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Date:
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24-Oct-07
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Release date:
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22-Jan-08
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PROCHECK
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Headers
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References
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P00918
(CAH2_HUMAN) -
Carbonic anhydrase 2 from Homo sapiens
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Seq:
Struc:
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260 a.a.
256 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.4.2.1.1
- carbonic anhydrase.
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Reaction:
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hydrogencarbonate + H+ = CO2 + H2O
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hydrogencarbonate
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+
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H(+)
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=
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CO2
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+
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H2O
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Cofactor:
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Zn(2+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Bioorg Med Chem Lett
18:152-158
(2008)
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PubMed id:
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Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.
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O.Güzel,
C.Temperini,
A.Innocenti,
A.Scozzafava,
A.Salman,
C.T.Supuran.
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ABSTRACT
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2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide was tested for its
interaction with 12 carbonic anhydrase (CA, EC 4.2.1.1) isoforms in the search
of compounds with good inhibitory activity against isozymes with medicinal
chemistry applications, such as CA I, II, VA, VB, VII, IX, and XII among others.
This sulfonamide is a potent inhibitor of CA I and II (K(I)s of 7.2-7.5 nM), a
medium potency inhibitor of CA VII, IX, XII, and XIV, and a weak inhibitor
against the other ubiquitous isoforms, making it thus a very interesting
clinical candidate for situations in which a strong inhibition of CA I and II is
needed. The crystal structure of the hCA II adduct of this sulfonamide revealed
many favorable interactions between the inhibitor and the enzyme which explain
its strong low nanomolar affinity for this isoform but may also be exploited for
the design of effective inhibitors incorporating bicyclic moieties.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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F.Carta,
B.Pothen,
A.Maresca,
M.Tiwari,
V.Singh,
and
C.T.Supuran
(2009).
Carbonic anhydrase inhibitors: inhibition of cytosolic carbonic anhydrase isozymes II and VII with simple aromatic sulfonamides and some azo dyes.
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Chem Biol Drug Des,
74,
196-202.
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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.
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Links
