Implications on zinc binding to S100A2


Dateien zu dieser Ressource

Dateien Größe Format Anzeige

Zu diesem Dokument gibt es keine Dateien.

KOCH, Michael, Shibani BHATTACHARYA, Torsten KEHL, Mario GIMONA, Milan VAŠÁK, Walter CHAZIN, Claus W. HEIZMANN, Peter M.H. KRONECK, Günter FRITZ, 2007. Implications on zinc binding to S100A2. In: Biochimica et Biophysica Acta (BBA) / Molecular Cell Research. 1773(3), pp. 457-470. ISSN 0167-4889. eISSN 1879-2596

@article{Koch2007-03Impli-38310, title={Implications on zinc binding to S100A2}, year={2007}, doi={10.1016/j.bbamcr.2006.12.006}, number={3}, volume={1773}, issn={0167-4889}, journal={Biochimica et Biophysica Acta (BBA) / Molecular Cell Research}, pages={457--470}, author={Koch, Michael and Bhattacharya, Shibani and Kehl, Torsten and Gimona, Mario and Vašák, Milan and Chazin, Walter and Heizmann, Claus W. and Kroneck, Peter M.H. and Fritz, Günter} }

Fritz, Günter Koch, Michael Koch, Michael Bhattacharya, Shibani Vašák, Milan Implications on zinc binding to S100A2 Chazin, Walter Bhattacharya, Shibani 2017-04-04T12:46:17Z 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 Ca<sup>2+</sup> S100A2 binds Zn<sup>2+</sup> with a high affinity. Studies have been carried out to investigate whether Zn<sup>2+</sup> acts as a regulatory ion for S100A2, as in the case of Ca<sup>2+</sup>. Using the method of competition with the Zn<sup>2+</sup> chelator 4-(2-pyridylazo)-resorcinol, an apparent Kd of 25 nM has been determined for Zn<sup>2+</sup> binding to S100A2. The affinity lies close to the range of intracellular free Zn<sup>2+</sup> concentrations, suggesting that S100A2 is able to bind Zn2+ in the nucleus. Two Zn<sup>2+</sup>-binding sites have been identified using site directed mutagenesis and several spectroscopic techniques with Cd<sup>2+</sup> and Co<sup>2+</sup> as probes. In site 1 Zn<sup>2+</sup> is bound by Cys21 and most likely by His 17. The binding of Zn<sup>2+</sup> in site 2 induces the formation of a tetramer, whereby the Zn<sup>2+</sup> is coordinated by Cys2 from each subunit. Remarkably, only binding of Zn<sup>2+</sup> to site 2 substantially weakens the affinity of S100A2 for Ca<sup>2+</sup>. Analysis of the individual Ca<sup>2+</sup>-binding constants revealed that the Ca<sup>2+</sup> 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 Zn<sup>2+</sup> and Ca<sup>2+</sup>, and suggest that Zn<sup>2+</sup> might deactivate S100A2 by inhibiting response to intracellular Ca2+ signals. Gimona, Mario Heizmann, Claus W. Chazin, Walter Heizmann, Claus W. Kehl, Torsten Kroneck, Peter M.H. Kehl, Torsten Fritz, Günter Kroneck, Peter M.H. Vašák, Milan Gimona, Mario 2007-03 eng 2017-04-04T12:46:17Z

Das Dokument erscheint in:

KOPS Suche


Mein Benutzerkonto