PMID:17239974
| Citation |
Koch, M, Bhattacharya, S, Kehl, T, Gimona, M, Vasák, M, Chazin, W, Heizmann, CW, Kroneck, PM and Fritz, G (2007) Implications on zinc binding to S100A2. Biochim. Biophys. Acta 1773:457-70 |
|---|---|
| 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. |
| Links |
PubMed Online version:10.1016/j.bbamcr.2006.12.006 |
| Keywords |
Amino Acid Motifs; Binding Sites; Calcium/chemistry; Calcium/metabolism; Chemotactic Factors/chemistry; Chemotactic Factors/genetics; Chemotactic Factors/metabolism; Circular Dichroism; Cobalt/chemistry; Cobalt/metabolism; Genetic Variation/genetics; Humans; Ligands; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Protein Binding; S100 Proteins/chemistry; S100 Proteins/genetics; S100 Proteins/metabolism; Tyrosine/chemistry; Tyrosine/metabolism; Zinc/chemistry; Zinc/metabolism |
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