3B4F

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

Summary for 3B4F

• Entry DOI: 10.2210/pdb3b4f/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, MERCURY (II) ION, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase, inhibitors, sulfonamide, acetylation, cytoplasm, disease mutation, lyase, metal-binding, polymorphism, zinc, lyase(oxo-acid)
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29885.42

Authors

Guzel, o.,Temperini, c.,Innocenti, a.,Scozzafava, A.,Salman, a.,Supuran, c.t. (deposition date: 2007-10-24, release date: 2008-01-22, Last modification date: 2023-08-30)

Primary citation

Guzel, O.,Temperini, C.,Innocenti, A.,Scozzafava, A.,Salman, A.,Supuran, C.T.
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, 2008

PubMed Abstract: 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.

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

Experimental method

X-RAY DIFFRACTION (1.89 Å)