Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8.

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.

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

Source

Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Florence), Italy.

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.

PMID:: 17314045; [PubMed - indexed for MEDLINE]

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PDB/2IT4

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Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with phosphates, carbamoyl phosphate, and the phosphonate antiviral drug foscarnet. [Bioorg Med Chem Lett. 2004]
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Review Design of zinc binding functions for carbonic anhydrase inhibitors.
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Cited by 1 PubMed Central article

Review Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. [Chem Rev. 2008]
Review Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
Krishnamurthy VM, Kaufman GK, Urbach AR, Gitlin I, Gudiksen KL, Weibel DB, Whitesides GM. Chem Rev. 2008 Mar; 108(3):946-1051.

Structures reported by this article

X Ray Structure Of The Complex Between Carbonic Anhydrase I And The Phosphonate Antiviral Drug Foscarnet

PDB: 2IT4

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2 Å

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Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal...
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 .

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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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