Implications on zinc binding to S100A2

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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. Available under: doi: 10.1016/j.bbamcr.2006.12.006

@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. Gimona, Mario Vašák, Milan 2007-03 2017-04-04T12:46:17Z eng

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