Interconversion of the ligand arrays in the CD and EF sites of oncomodulin. Influence on Ca2+-binding affinity

Biochemistry
Michael T HenzlJ J Likos

Abstract

The parvalbumin metal ion-binding sites differ at the +z and -x residues: Whereas the CD site employs serine and glutamate (or aspartate), respectively, the EF site employs aspartate and glycine. Although frequently indistinguishable in Ca2+- and Mg2+-binding assays, the CD and EF sites nonetheless exhibit markedly different preferences for members of the lanthanide series [Williams et al. (1984) J. Am. Chem. Soc. 106, 5698-5702], underscoring an intrinsic nonequivalence. This nonequivalence reaches its pinnacle in the mammalian beta-parvalbumin (oncomodulin). Whereas the oncomodulin EF site exhibits the expected Ca2+/Mg2+ signature, the Ca2+ affinity of the CD site is severely attenuated. To obtain insight into the structural factors responsible for this reduction in binding affinity, oncomodulin variants were examined in which the CD and EF site ligand arrays had been exchanged. Our data suggest that binding affinity may be dictated either by ligand identity or by the binding site environment. For example, the Ca2+ affinity of the quasi-EF site resulting from the combined S55D and D59G mutations is substantially lower than that of the authentic EF site. This finding implies that other local environmental variables (e.g., bind...Continue Reading

References

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Citations

Feb 9, 2008·Proteins·Sergei E PermyakovEugene A Permyakov
Mar 29, 2005·Biophysical Chemistry·Kenosha F HobsonSusan Pedigo
Mar 18, 2005·Journal of the American Chemical Society·Yiming YeJenny J Yang

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