Poly-L-proline type II peptide mimics as probes of the active site occupancy requirements of cGMP-dependent protein kinase

R. Zhang, C. K. Nicki, A. Marnai, S. Flemer, A. Natarajan, W. R. Dostmann, J. S. Madalengoitia

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Based on the X-ray crystal structure of cAMP-dependent protein kinase (PKA) with the endogenous inhibitor PKI and the X-ray crystal structure of cyclin-dependent kinase 2 (CDK2) with a substrate peptide, a proposal is put forth that some protein kinases bind peptide substrates in their active sites in the poly-L-proline type II (PPII) conformation. In this work, PPII peptide mimics are evaluated as pseudosubstrate inhibitors of cGMP-dependent protein kinase (PKG) to explore if PKG also binds peptide substrates in the PPII conformation. Inhibition data of our PPII mimetics provide evidence that the P - 1, P - 2, and P - 3 residues of substrate peptides bind in the PPII conformation (Φ approximately -75°, ψ approximately 145°). In addition, the inhibition data also suggest that the P - 1, P - 2, and P - 3 residues in substrate peptides bind with a gauche(-) χ1 angle. Copyright Blackwell Munksgaard, 2005.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalJournal of Peptide Research
Volume66
Issue number4
DOIs
StatePublished - Oct 2005

Keywords

  • PKG
  • Peptide mimics
  • Poly-L-proline
  • Protein kinase

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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