2it4

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==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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[[Category: Innocenti, A.]]
[[Category: Innocenti, A.]]
[[Category: Scozzafava, A.]]
[[Category: Scozzafava, A.]]
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[[Category: Supuran, C.T.]]
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[[Category: Supuran, C T.]]
[[Category: Temperini, C.]]
[[Category: Temperini, C.]]
[[Category: PPF]]
[[Category: PPF]]
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[[Category: lyase]]
[[Category: lyase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:39:18 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:55:42 2008''

Revision as of 15:55, 21 February 2008


2it4, resolution 2.0Å

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

Overview

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.

About this Structure

2IT4 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.

Reference

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, Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. PMID:17314045

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