Implications on zinc binding to S100A2.

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Koch M, Bhattacharya S, Kehl T, Gimona M, Vasak M, Chazin W, Heizmann CW, Kroneck PM, Fritz G

Implications on zinc binding to S100A2.

Biochim Biophys Acta. 2007 Mar;1773(3):457-70. Epub 2006 Dec 19.

PubMed ID

17239974 [ View in PubMed

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Abstract

Human S100A2 is an EF-hand calcium-binding S100 protein that is localized mainly in the nucleus and functions as tumor suppressor. In addition to Ca2+ S100A2 binds Zn2+ with a high affinity. Studies have been carried out to investigate whether Zn2+ acts as a regulatory ion for S100A2, as in the case of Ca2+. Using the method of competition with the Zn2+ chelator 4-(2-pyridylazo)-resorcinol, an apparent Kd of 25 nM has been determined for Zn2+ binding to S100A2. The affinity lies close to the range of intracellular free Zn2+ concentrations, suggesting that S100A2 is able to bind Zn2+ in the nucleus. Two Zn2+-binding sites have been identified using site directed mutagenesis and several spectroscopic techniques with Cd2+ and Co2+ as probes. In site 1 Zn2+ is bound by Cys21 and most likely by His 17. The binding of Zn2+ in site 2 induces the formation of a tetramer, whereby the Zn(2+) is coordinated by Cys2 from each subunit. Remarkably, only binding of Zn2+ to site 2 substantially weakens the affinity of S100A2 for Ca2+. Analysis of the individual Ca2+-binding constants revealed that the Ca2+ affinity of one EF-hand is decreased about 3-fold, whereas the other EF-hand exhibits a 300-fold decrease in affinity. These findings imply that S100A2 is regulated by both Zn2+ and Ca2+, and suggest that Zn2+ might deactivate S100A2 by inhibiting response to intracellular Ca2+ signals.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Calcium	Protein S100-A2	Protein	Humans	Unknown	Not Available	Details
Zinc	Protein S100-A2	Protein	Humans	Unknown	Not Available	Details
Zinc acetate	Protein S100-A2	Protein	Humans	Unknown	Not Available	Details
Zinc chloride	Protein S100-A2	Protein	Humans	Unknown	Inactivator Regulator	Details
Zinc sulfate, unspecified form	Protein S100-A2	Protein	Humans	Unknown	Inactivator Regulator	Details