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 language | English (US) |
---|---|
Pages (from-to) | 151-159 |
Number of pages | 9 |
Journal | Journal of Peptide Research |
Volume | 66 |
Issue number | 4 |
DOIs | |
State | Published - Oct 1 2005 |
Fingerprint
Keywords
- PKG
- Peptide mimics
- Poly-L-proline
- Protein kinase
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
Cite this
Poly-L-proline type II peptide mimics as probes of the active site occupancy requirements of cGMP-dependent protein kinase. / Zhang, R.; Nicki, C. K.; Marnai, A.; Flemer, S.; Natarajan, A.; Dostmann, W. R.; Madalengoitia, J. S.
In: Journal of Peptide Research, Vol. 66, No. 4, 01.10.2005, p. 151-159.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Poly-L-proline type II peptide mimics as probes of the active site occupancy requirements of cGMP-dependent protein kinase
AU - Zhang, R.
AU - Nicki, C. K.
AU - Marnai, A.
AU - Flemer, S.
AU - Natarajan, A.
AU - Dostmann, W. R.
AU - Madalengoitia, J. S.
PY - 2005/10/1
Y1 - 2005/10/1
N2 - 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.
AB - 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.
KW - PKG
KW - Peptide mimics
KW - Poly-L-proline
KW - Protein kinase
UR - http://www.scopus.com/inward/record.url?scp=25144436860&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25144436860&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3011.2005.00280.x
DO - 10.1111/j.1399-3011.2005.00280.x
M3 - Article
C2 - 16138853
AN - SCOPUS:25144436860
VL - 66
SP - 151
EP - 159
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 4
ER -