ABSTRACT
Cupredoxins are the perfect model proteins to dissect and understand the structure-function relationship in T1 centres. In the last decades the Coupled Distortion Model (CDM) has been the only reference to describe the structure-function relationship in T1 centres. The discovery of novel cupredoxins demonstrates their high diversity, with variations in term of copper-binding ligands, copper centre geometry, redox potential, as well as biological function. AcoP is a periplasmic cupredoxin belonging to the iron respiratory chain of an acidophilic bacterium [1]. It presents original features, including high resistance to acidic pH and a green-type copper center of high redox potential [2]. In this study [3], structural and biophysical characterization of wild-type AcoP and of two Cu-ligand mutants (H166A and M171A) confirms that the active centre of AcoP is highly constrained. Comparative analysis with other cupredoxins of known structures, suggests that in AcoP the second coordination sphere might be the main determinant of active centre rigidity, due to the presence of an extensive hydrogen bond network. Crystallographic structures of native reduced (1.65 Å resolution) and oxidized AcoP, confirmed by EXAFS data, unveil unusual Cu-ligand distances , presenting both T1 and T1.5 features. This finding suggests that for AcoP the CDM might not hold valid. Finally we show that for other cupredoxins as well, the properties described do not fit well the CDM, and propose that alternative models describing Cu centre geometries need to be developed, while the importance of rack-induced contributions should not be underestimated.
[1] M. Roger et al., PLoS One. 2014, 9, e98941.
[2] M. Roger et al., BBA Bioenerg. 2017, 1858, 351-359.
[3] M. Roger et al., Dalton Trans. 2024, 53, 1794-1808.