cAMP-Dependent Protein Kinase
2010; Elsevier BV; Linguagem: Inglês
10.1016/b978-0-12-374145-5.00179-0
AutoresSusan S. Taylor, Elzbieta Radzio‐Andzelm,
Tópico(s)Cell death mechanisms and regulation
ResumoThis chapter sheds light on the structure of the catalytic (C) subunit that serves as a structural prototype for the entire protein kinase family and explains the structure of the dimerization/docking domain of RIIα. Three isoforms of the C subunit have been identified in mammals that include α, β, and γ. The Cα subunit is expressed constitutively in all cells, whereas expression of Cβ is tissue-specific, and especially prominent in brain. Cγ is found primarily in testes. The C subunit is a highly concerted enzyme and all its energy is focused on transferring the γ-phosphate of ATP to an appropriate substrate protein. There are two general recognition motifs for protein kinase (PKA) substrates, Arg-Arg-X-Ser/Thr-Hyd and Arg-X-X-Arg-X-X-Ser/Thr-Hyd, where X is any residue and Hyd is a hydrophobic residue. The C subunit comprises a highly conserved core containing a smaller ATP binding domain that is dominated by β structure, and a larger, mostly helical lobe that provides a docking site for peptides/proteins as well as several essential residues that contribute to catalysis. The adenine ring of ATP is buried at the base of the cleft between the two lobes, and the peptide docks to the surface of the large lobe at the edge of the cleft. All mammalian regulatory (R) subunits share the same organization. At the N-terminus is a dimerization/docking domain that locks the enzyme into a stable dimmer. In the RI subunits, the two protomers are actually linked by a disulfide bond. This is followed by a flexible and variable linker region that also contains a pseudo-substrate inhibitor site.
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