2IT4

X ray structure of the complex between Carbonic Anhydrase I and the phosphonate antiviral drug foscarnet

Summary for 2IT4

• Entry DOI: 10.2210/pdb2it4/pdb
• Descriptor: Carbonic anhydrase 1, ZINC ION, PHOSPHONOFORMIC ACID, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase, antiviral, crystal stucture, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00915
• Total number of polymer chains: 2
• Total formula weight: 57066.08

Authors

Temperini, C.,Innocenti, A.,Guerri, A.,Scozzafava, A.,Supuran, C.T. (deposition date: 2006-10-19, release date: 2007-09-11, Last modification date: 2023-08-30)

Primary citation

Temperini, C.,Innocenti, A.,Guerri, A.,Scozzafava, A.,Rusconi, S.,Supuran, C.T.
Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I.
Bioorg.Med.Chem.Lett., 17:2210-2215, 2007

PubMed Abstract: Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment of HIV and herpes virus infections, also acts as an activator or inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Interaction of the drug with 11 CA isozymes has been investigated kinetically, and the X-ray structure of its adduct with isoform I (hCA I-foscarnet complex) has been resolved. The first CA inhibitor possessing a phosphonate zinc-binding group is thus evidenced, together with the factors governing recognition of such small molecules by a metalloenzyme active site. Foscarnet is also a clear-cut example of modulator of an enzyme activity which can act either as an activator or inhibitor of a CA isozyme.

PubMed: 17314045
DOI: 10.1016/j.bmcl.2007.01.113

Experimental method

X-RAY DIFFRACTION (2 Å)