Showing papers by "Barbara Guerra published in 1999"
TL;DR: The structure of the catalytic subunit with the fixed positioning of the activation segment in the active conformation through its own aminoterminal region suggests a regulation at the transcriptional level making a regulation by second messengers unlikely.
Abstract: Protein kinase CK2 is a pleiotropic, ubiquitous and constitutively active protein kinase that can use both ATP and GTP as phosphoryl donors with specificity for serine/threonine residues in the vicinity of acidic amino acids. Recent results show that the enzyme is involved in transcription, signaling, proliferation and in various steps of development. The tetrameric holoenzyme (alpha2beta2) consists of two catalytic alpha-subunits and two regulatory beta-subunits. The structure of the catalytic subunit with the fixed positioning of the activation segment in the active conformation through its own aminoterminal region suggests a regulation at the transcriptional level making a regulation by second messengers unlikely. The high conservation of the catalytic subunit from yeast to man and its role in the tetrameric complex supports this notion. The regulatory beta-subunit has been far less conserved throughout evolution. Furthermore the existence of different CK2beta-related proteins together with the observation of deregulated CK2beta levels in tumor cells and the reported association of CK2beta protein with key proteins in signal transduction, e.g. A-Raf, Mos, pg90rsk etc. are suggestive for an additional physiological role of CK2beta protein beside being the regulatory compound in the tetrameric holoenzyme.
389 citations
TL;DR: The structures of the catalytic subunit of protein kinase CK2 from Zea mays complexed with Mg2+ and with analogs of ATP or GTP were determined and demonstrate that water molecules are critical to switch the active site of CK1 from an ATP- to a GTP-compatible state.
Abstract: The structures of the catalytic subunit of protein kinase CK2 from Zea mays complexed with Mg2+ and with analogs of ATP or GTP were determined to 2.2 A resolution. Unlike most other protein kinases, CK2 from various sources shows 'dual-cosubstrate specificity', that is, the ability to efficiently use either ATP or GTP as a cosubstrate. The structures of these complexes demonstrate that water molecules are critical to switch the active site of CK2 from an ATP- to a GTP-compatible state. An understanding of the structural basis of dual-cosubstrate specificity may help in the design of drugs that target CK2 or other kinases with this property.
180 citations
TL;DR: Results from the immunoprecipitation experiments support the notion for the existence of a ‘free CK2β’ (or in complex with proteins other than CK2 α) in normal animal tissue apart from the hitherto dogmatic association with CK2α in a tetrameric holoenzyme complex.
123 citations
TL;DR: In this article, the structure-function relationship of protein kinase CK2 has been investigated and the structure features responsible for high basal activity and for unusual response to nucleotide analogs have been revealed.
87 citations
TL;DR: It is concluded that cisplatin and its second generation drug carboplatin act similarly i.e. both drugs cause a concomitant decrease in p53 mRNA and an increase in p 53 protein level after 4 h treatment with either of the two drugs.
22 citations