Blue copper proteins are type-I copper-containing redox proteins whose role is to shuttle electrons from an electron donor to an electron acceptor in bacteria and plants. A large amount of experimental data is available on blue copper proteins; however, their functional characterization is hindered by the complexity of redox processes in biological systems. We describe here the application of a semiquantitative method based on a comparative analysis of molecular interaction fields to gain insights into the recognition properties of blue copper proteins. Molecular electrostatic and hydrophobic potentials were computed and compared for a set of 33 experimentally-determined structures of proteins from seven blue copper subfamilies, and the results were quantified by means of similarity indices. The analysis provides a classification of the blue copper proteins and shows that~1! comparison of the molecular electrostatic potentials provides useful information complementary to that highlighted by sequence analysis;~2! similarities in recognition properties can be detected for proteins belonging to different subfamilies, such as amicyanins and pseudoazurins, that may be isofunctional proteins;~3! dissimilarities in interaction properties, consistent with experimentally different binding specificities, may be observed between proteins belonging to the same subfamily, such as cyanobacterial and eukaryotic plastocyanins;~4! proteins with low sequence identity, such as azurins and pseudoazurins, can have sufficient similarity to bind to similar electron donors and acceptors while having different binding specificity profiles.Keywords: blue copper proteins; electrostatic potential; electron transfer; hydrophobic potential; protein-protein interactions; redox proteins; similarity index Blue copper proteins, which are also known as cupredoxins, are small, soluble proteins~10-14 kDa! whose active site contains a type-I copper. As far as it is known, they exert their function by shuttling electrons from a protein acting as an electron donor to another acting as an electron acceptor in various biological systems, such as bacterial and plant photosynthesis~Baker, 1994; Sykes, 1994!.A large amount of structural and spectroscopic data is available for the blue copper proteins, which have been named and classified into subfamilies according to their spectroscopic properties~Ad-man, 1991!. High resolution X-ray and NMR structures are known for several members of each of the plastocyanin, azurin, pseudoazurin, and amicyanin subfamilies~Baker, 1994!, and for single members of three further subfamilies, the rusticyanins~Harvey et al., 1998!, the cucumber basic proteins~CBP!~Guss et al., 1996!, and the stellacyanins~Hart et al., 1996!. Despite often showing low~Ͻ20%! sequence identity, all these proteins possess an eight-stranded Greek key b-barrel or b-sandwich fold and have a highly conserved active site architecture~Baker, 1994; Sykes, 1994!. Important information concerning the functional role and the binding properties of th...

ABSTRACT:We describe how similarity indices may be applied to semiquantitatively compare the molecular interaction fields, such as electrostatic and hydrophobic potentials, of proteins. We then review ways in which this approach has been used to investigate protein interaction properties in diverse applications ranging from in-depth comparison of pairs of proteins to large-scale analysis of hundreds of modeled protein structures.

The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with CPHD and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient-referring population.