ISDA: 3B4F

Deposition Date 2007-10-24

Release Date 2008-01-22

Last Version Date 2023-08-30

Entry Detail

PDB ID:

3B4F

Keywords:

LYASE

Title:

Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.89 Å

R-Value Free:

0.23

R-Value Work:

0.19

R-Value Observed:

0.19

Space Group:

P 1 21 1

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Macromolecular Entities

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:Carbonic anhydrase 2
Gene (Uniprot):CA2
Chain IDs:A
Chain Length:260
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:P00918 Pfam ID:PF00194 EC:4.2.1.1

Ligand Molecules

TUO

Primary Citation

Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies.

Guzel, O, Temperini, C, Innocenti, A, Scozzafava, A, Salman, A, Supuran, C.T.Show

Bioorg. Med. Chem. Lett. 18 152 158 (2008)

PMID: 18024029 DOI: 10.1016/j.bmcl.2007.10.110

Abstact

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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Chemical

Disease

Primary Citation of related structures

Abstact

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