PDBsum entry 2it4

Lyase

PDB id

2it4

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Contents

			Protein chains

					256 a.a. *

			Ligands

					PPF

			Metals

					_ZN ×2

			Waters ×344

* Residue conservation analysis

PDB id:

2it4

Links

Name:

Lyase

Title:

X ray structure of the complex between carbonic anhydrase i and the phosphonate antiviral drug foscarnet

Structure:

Carbonic anhydrase 1. Chain: a, b. Synonym: carbonic anhydrase i, carbonate dehydratase i, ca-i. Ec: 4.2.1.1

Source:

Homo sapiens. Human. Organism_taxid: 9606

Resolution:

2.00Å

R-factor:

0.249

R-free:

0.316

Authors:

C.Temperini,A.Innocenti,A.Guerri,A.Scozzafava,C.T.Supuran

Key ref:

C.Temperini et al. (2007). 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. PubMed id: 17314045 DOI: 10.1016/j.bmcl.2007.01.113

Date:

19-Oct-06

Release date:

11-Sep-07

PROCHECK

	Headers

	References

Protein chains

P00915 (CAH1_HUMAN) - Carbonic anhydrase 1 from Homo sapiens

Seq: Struc:					261 a.a. 256 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.4.2.1.1 - carbonic anhydrase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

hydrogencarbonate + H⁺ = CO2 + H2O

hydrogencarbonate

H(+)

CO2
Bound ligand (Het Group name = PPF)
matches with 42.86% similarity

H2O

Cofactor:

Zn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.bmcl.2007.01.113	Bioorg Med Chem Lett 17:2210-2215 (2007)
PubMed id: 17314045

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

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20505865

V.Alterio, S.M.Monti, E.Truppo, C.Pedone, C.T.Supuran, and G.De Simone (2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.

Org Biomol Chem, 8, 3528-3533.

PDB code:

3lxe

18335973

V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.

Chem Rev, 108, 946.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.