Conformational Analysis of PKI(5-22)amide, the Active Inhibitory Fragment of the Inhibitor Protein of the Cyclic AMP-dependent Protein Kinase

Overview

Journal Biochem J

Specialty Biochemistry

Date 1989 Dec 1

PMID 2604724

Citations 11

Authors

J Reed

J S de Ropp

J Trewhella

D B Glass

W K Liddle

E M Bradbury

V Kinzel

D A Walsh

Affiliations

Soon will be listed here.

Abstract

Fourier-transform i.r. spectroscopy, 1H-n.m.r. spectroscopy and X-ray scattering were used to study the conformation and shape of the peptide PKI(5-22)amide, which contains the active site of the inhibitor protein of the cyclic AMP-dependent protein kinase [Cheng, Van Pattern, Smith & Walsh (1985) Biochem. J. 231, 655-661]. The X-ray-scattering solution studies show that the peptide has a compact structure with Rg 0.9 nm (9.0 A) and a linear maximum dimension of 2.5 nm (25A). Compatible with this, Fourier-transform i.r. and n.m.r. determinations indicate that the peptide contains approx. 26% alpha-helix located in the N-terminal one-third of the molecule. This region contains the phenylalanine residue that is one essential recognition determinant for high-affinity binding to the protein kinase catalytic site.

Citing Articles

Role of the αC-β4 loop in protein kinase structure and dynamics.

Wu J, Jonniya N, Hirakis S, Olivieri C, Veglia G, Kornev A Elife. 2024; 12.

PMID: 39630082 PMC: 11616992. DOI: 10.7554/eLife.91980.

Redox Modification of PKA-Cα Differentially Affects Its Substrate Selection.

Delva-Wiley J, Ekhator E, Adams L, Patwardhan S, Dong M, Newman R Life (Basel). 2023; 13(9).

PMID: 37763215 PMC: 10532679. DOI: 10.3390/life13091811.

Protein Kinase Structure and Dynamics: Role of the αC-β4 Loop.

Wu J, Jonniya N, Hirakis S, Olivieri C, Veglia G, Kornev A bioRxiv. 2023; .

PMID: 37693538 PMC: 10491255. DOI: 10.1101/2023.08.31.555822.

Edmond Fischer's kinase legacy: History of the protein kinase inhibitor and protein kinase A.

Taylor S, Herberg F, Veglia G, Wu J IUBMB Life. 2023; 75(4):311-323.

PMID: 36855225 PMC: 10050139. DOI: 10.1002/iub.2714.

Biochemical Analysis of AKAP-Anchored PKA Signaling Complexes.

Byrne D, Omar M, Kennedy E, Eyers P, Scott J Methods Mol Biol. 2022; 2483:297-317.

PMID: 35286684 PMC: 9518671. DOI: 10.1007/978-1-0716-2245-2_19.

References

Walsh D, Ashby C, Gonzalez C, Calkins D, FISCHER E . Krebs EG: Purification and characterization of a protein inhibitor of adenosine 3',5'-monophosphate-dependent protein kinases. J Biol Chem. 1971; 246(7):1977-85. View

Glass D, Lundquist L, Katz B, Walsh D . Protein kinase inhibitor-(6-22)-amide peptide analogs with standard and nonstandard amino acid substitutions for phenylalanine 10. Inhibition of cAMP-dependent protein kinase. J Biol Chem. 1989; 264(24):14579-84. View

Gill G, Holdy K, Walton G, Kanstein C . Purification and characterization of 3':5'-cyclic GMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1976; 73(11):3918-22. PMC: 431265. DOI: 10.1073/pnas.73.11.3918. View

Demaille J, Peters K, FISCHER E . Isolation and properties of the rabbit skeletal muscle protein inhibitor of adenosine 3',5'-monophosphate dependent protein kinases. Biochemistry. 1977; 16(14):3080-6. DOI: 10.1021/bi00633a006. View

Chou P, Fasman G . Empirical predictions of protein conformation. Annu Rev Biochem. 1978; 47:251-76. DOI: 10.1146/annurev.bi.47.070178.001343. View

Granot J, Mildvan A, Bramson H, Thomas N, Kaiser E . Nuclear magnetic resonance studies of the conformation and kinetics of the peptide-substrate at the active site of bovine heart protein kinase. Biochemistry. 1981; 20(3):602-10. DOI: 10.1021/bi00506a024. View

Nagayama K, Wuthrich K . Structural interpretation of vicinal proton-proton coupling constants 3JH alpha H beta in the basic pancreatic trypsin inhibitor measured by two-dimensional J-resolved NMR spectroscopy. Eur J Biochem. 1981; 115(3):653-7. DOI: 10.1111/j.1432-1033.1981.tb06252.x. View

Chou P, Fasman G . Prediction of beta-turns. Biophys J. 1979; 26(3):367-83. PMC: 1328558. DOI: 10.1016/S0006-3495(79)85259-5. View

Gariepy J, Sykes B, Reid R, Hodges R . Proton nuclear magnetic resonance investigation of synthetic calcium-binding peptides. Biochemistry. 1982; 21(7):1506-12. DOI: 10.1021/bi00536a007. View

10.

Levinson B, Pickover C, Richards F . Dimerization by colicin E3 in the absence of immunity protein. J Biol Chem. 1983; 258(18):10967-72. View

11.

Pardi A, Billeter M, Wuthrich K . Calibration of the angular dependence of the amide proton-C alpha proton coupling constants, 3JHN alpha, in a globular protein. Use of 3JHN alpha for identification of helical secondary structure. J Mol Biol. 1984; 180(3):741-51. DOI: 10.1016/0022-2836(84)90035-4. View

12.

Scott J, FISCHER E, Takio K, Demaille J, KREBS E . Amino acid sequence of the heat-stable inhibitor of the cAMP-dependent protein kinase from rabbit skeletal muscle. Proc Natl Acad Sci U S A. 1985; 82(17):5732-6. PMC: 390626. DOI: 10.1073/pnas.82.17.5732. View

13.

Cheng H, Van Patten S, Smith A, Walsh D . An active twenty-amino-acid-residue peptide derived from the inhibitor protein of the cyclic AMP-dependent protein kinase. Biochem J. 1985; 231(3):655-61. PMC: 1152799. DOI: 10.1042/bj2310655. View

14.

Cheng H, Kemp B, Pearson R, Smith A, Misconi L, Van Patten S . A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase. J Biol Chem. 1986; 261(3):989-92. View

15.

Scott J, Glaccum M, FISCHER E, KREBS E . Primary-structure requirements for inhibition by the heat-stable inhibitor of the cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1986; 83(6):1613-6. PMC: 323133. DOI: 10.1073/pnas.83.6.1613. View

16.

Byler D, SUSI H . Examination of the secondary structure of proteins by deconvolved FTIR spectra. Biopolymers. 1986; 25(3):469-87. DOI: 10.1002/bip.360250307. View

17.

Glass D, Cheng H, Kemp B, Walsh D . Differential and common recognition of the catalytic sites of the cGMP-dependent and cAMP-dependent protein kinases by inhibitory peptides derived from the heat-stable inhibitor protein. J Biol Chem. 1986; 261(26):12166-71. View

18.

Reed J, Kinzel V, Cheng H, Walsh D . Circular dichroic investigations of secondary structure in synthetic peptide inhibitors of cAMP-dependent protein kinase: a model for inhibitory potential. Biochemistry. 1987; 26(24):7641-7. DOI: 10.1021/bi00398a017. View

19.

Heidorn D, Trewhella J . Comparison of the crystal and solution structures of calmodulin and troponin C. Biochemistry. 1988; 27(3):909-15. DOI: 10.1021/bi00403a011. View

20.

Trewhella J, Liddle W, Heidorn D, Strynadka N . Calmodulin and troponin C structures studied by Fourier transform infrared spectroscopy: effects of Ca2+ and Mg2+ binding. Biochemistry. 1989; 28(3):1294-301. DOI: 10.1021/bi00429a052. View