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.

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Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT

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. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8.

PubMed ID
17314045 [ View in 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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Carbonic anhydrase 1P00915Details
Carbonic anhydrase 2P00918Details
Carbonic anhydrase 4P22748Details
Carbonic anhydrase 12O43570Details
Carbonic anhydrase 9Q16790Details
Carbonic anhydrase 5A, mitochondrialP35218Details
Carbonic anhydrase 5B, mitochondrialQ9Y2D0Details
Carbonic anhydrase 6P23280Details
Carbonic anhydrase 7P43166Details
Carbonic anhydrase 14Q9ULX7Details