J 2016

Allosteric Effect of Adenosine Triphosphate on Peptide Recognition by 3 ' 5 '-Cyclic Adenosine Monophosphate Dependent Protein Kinase Catalytic Subunits

KIVI, Rait, Karina SOLOVJOVA, Tiv HALJASORG, Piret ARUKUUSK, Jaak JARV et. al.

Basic information

Original name

Allosteric Effect of Adenosine Triphosphate on Peptide Recognition by 3 ' 5 '-Cyclic Adenosine Monophosphate Dependent Protein Kinase Catalytic Subunits

Authors

KIVI, Rait (233 Estonia), Karina SOLOVJOVA (233 Estonia, guarantor, belonging to the institution), Tiv HALJASORG (233 Estonia), Piret ARUKUUSK (233 Estonia) and Jaak JARV (233 Estonia)

Edition

The Protein Journal, NEW YORK, SPRINGER, 2016, 1572-3887

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 1.139

RIV identification code

RIV/00216224:14740/16:00093864

Organization unit

Central European Institute of Technology

UT WoS

000389918500008

Keywords in English

cAMP-dependent protein kinase catalytic subunit; Allosteric regulation mechanism; ATP binding; Peptide binding; Ligand structure effect

Tags

Změněno: 10/3/2017 08:55, Mgr. Eva Špillingová

Abstract

V originále

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.