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Research Database PMU-SQQUID

Implications on zinc binding to S100A2.
Koch, M; Bhattacharya, S; Kehl, T; Gimona, M; Vasák, M; Chazin, W; Heizmann, CW; Kroneck, PM; Fritz, G;
Biochim Biophys Acta. 2007; 1773(3):45-70
Originalarbeiten (Zeitschrift)

PMU-Authors

Gimona Mario

Abstract

Human S100A2 is an EF-hand calcium-binding S 100 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 K-d 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 Zn2+ 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. (c) 2006 Elsevier BX All rights reserved.


Useful keywords (using NLM MeSH Indexing)

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*


Find related publications in this database (Keywords)

S100
S100A2
zinc
calcium
cobalt