1SMH

Protein kinase A variant complex with completely ordered N-terminal helix

Summary for 1SMH

• Entry DOI: 10.2210/pdb1smh/pdb
• Descriptor: cAMP-Dependent Protein Kinase, alpha-catalytic subunit, cAMP-dependent protein kinase inhibitor, alpha form, (R,R)-2,3-BUTANEDIOL, ... (5 entities in total)
• Functional Keywords: pka; protein kinase a; camp-dependent protein kinase; phosphorylation; ser10; myristoylation; posttranslational modification; signaling; membrane, alpha helix, signaling protein, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Bos taurus (cattle); More
• Cellular location: Cytoplasm: P00517
• Total number of polymer chains: 2
• Total formula weight: 43751.92

Authors

Breitenlechner, C.,Engh, R.A.,Huber, R.,Kinzel, V.,Bossemeyer, D.,Gassel, M. (deposition date: 2004-03-09, release date: 2004-07-06, Last modification date: 2024-10-30)

Primary citation

Breitenlechner, C.,Engh, R.A.,Huber, R.,Kinzel, V.,Bossemeyer, D.,Gassel, M.
The Typically Disordered N-Terminus of PKA Can Fold as a Helix and Project the Myristoylation Site into Solution
Biochemistry, 43:7743-7749, 2004

PubMed Abstract: Protein kinases comprise the major enzyme family critically involved in signal transduction pathways; posttranslational modifications affect their regulation and determine signaling states. The prototype protein kinase A (PKA) possesses an N-terminal alpha-helix (Helix A) that is atypical for kinases and is thus a major distinguishing feature of PKA. Its physiological function may involve myristoylation at the N-terminus and modulation via phosphorylation at serine 10. Here we describe an unusual structure of an unmyristoylated PKA, unphosphorylated at serine 10, with a completely ordered N-terminus. Using standard conditions (e.g., PKI 5-24, ATP site ligand, MEGA-8), a novel 2-fold phosphorylated PKA variant showed the ordered N-terminus in a new crystal packing arrangement. Thus, the critical factor for structuring the N-terminus is apparently the absence of phosphorylation of Ser10. The flexibility of the N-terminus, its myristoylation, and the conformational dependence on the phosphorylation state are consistent with a functional role for myristoylation.

PubMed: 15196017
DOI: 10.1021/bi0362525

Experimental method

X-RAY DIFFRACTION (2.044 Å)