2qvs
From Proteopedia
Crystal Structure of Type IIa Holoenzyme of cAMP-dependent Protein Kinase
Overview
The catalytic (C) subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is inhibited by two classes of regulatory subunits, RI and RII. The RII subunits are substrates as well as inhibitors and do not require adenosine triphosphate (ATP) to form holoenzyme, which distinguishes them from RI subunits. To understand the molecular basis for isoform diversity, we solved the crystal structure of an RIIalpha holoenzyme and compared it to the RIalpha holoenzyme. Unphosphorylated RIIalpha(90-400), a deletion mutant, undergoes major conformational changes as both of the cAMP-binding domains wrap around the C subunit's large lobe. The hallmark of this conformational reorganization is the helix switch in domain A. The C subunit is in an open conformation, and its carboxyl-terminal tail is disordered. This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA.
About this Structure
2QVS is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity., Wu J, Brown SH, von Daake S, Taylor SS, Science. 2007 Oct 12;318(5848):274-9. PMID:17932298 Page seeded by OCA on Sun May 4 15:46:29 2008
Categories: Mus musculus | Protein complex | CAMP-dependent protein kinase | Brown, S H.J. | Daake, S von. | Taylor, S S. | Wu, J. | Acetylation | Alternative splicing | Atp-binding | Camp-binding | Camp-dependent protein kinase | Crystal structure | Cytoplasm | Isoform diversity | Lipoprotein | Myristate | Nucleotide-binding | Nucleus | Phosphorylation | Serine/threonine-protein kinase | Transferase | Transferase/transferase regulator complex | Type iia holoenzyme
