Allosteric Effect of Adenosine Triphosphate on Peptide Recognition by 3'5'-Cyclic Adenosine Monophosphate Dependent Protein Kinase Catalytic Subunits
Language English Country Netherlands Media print
Document type Journal Article
PubMed
27848106
DOI
10.1007/s10930-016-9691-9
PII: 10.1007/s10930-016-9691-9
Knihovny.cz E-resources
- Keywords
- ATP binding, Allosteric regulation mechanism, Ligand structure effect, Peptide binding, cAMP-dependent protein kinase catalytic subunit,
- MeSH
- 2-Naphthylamine analogs & derivatives chemistry MeSH
- Adenosine Triphosphate chemistry metabolism MeSH
- Allosteric Regulation MeSH
- Allosteric Site MeSH
- Cyclic AMP chemistry metabolism MeSH
- Staining and Labeling methods MeSH
- Fluorescent Dyes chemistry MeSH
- Protein Kinase Inhibitors chemistry metabolism MeSH
- Catalytic Domain MeSH
- Kinetics MeSH
- Humans MeSH
- Ligands MeSH
- Peptides chemistry metabolism MeSH
- Cyclic AMP-Dependent Protein Kinases chemistry metabolism MeSH
- Amino Acid Sequence MeSH
- Thermodynamics MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 2-Naphthylamine MeSH
- acrylodan MeSH Browser
- Adenosine Triphosphate MeSH
- Cyclic AMP MeSH
- Fluorescent Dyes MeSH
- Protein Kinase Inhibitors MeSH
- Ligands MeSH
- Peptides MeSH
- Cyclic AMP-Dependent Protein Kinases MeSH
The allosteric influence of adenosine triphosphate (ATP) on the binding effectiveness of a series of peptide inhibitors with the catalytic subunit of 3'5'-cyclic adenosine monophosphate dependent protein kinase was investigated, and the dependence of this effect on peptide structure was analyzed. The allosteric effect was calculated as ratio of peptide binding effectiveness with the enzyme-ATP complex and with the free enzyme, quantified by the competitive inhibition of the enzyme in the presence of ATP excess, and by the enzyme-peptide complex denaturation assay, respectively It was found that the principle "better binding-stronger allostery" holds for interactions of the studied peptides with the enzyme, indicating that allostery and peptide binding with the free enzyme are governed by the same specificity pattern. This means that the allosteric regulation does not include new ligand-protein interactions, but changes the intensity (strength) of the interatomic forces that govern the complex formation in the case of each individual ligand. We propose that the allosteric regulation can be explained by the alteration of the intrinsic dynamics of the protein by ligand binding, and that this phenomenon, in turn, modulates the ligand off-rate from its binding site as well as the binding affinity. The positive allostery could therefore be induced by a reduction in the enzyme's overall intrinsic dynamics.
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