Physical Nature of Intermolecular Interactions within cAMP-Dependent Protein Kinase Active Site: Differential Transition State Stabilization in Phosphoryl Transfer Reaction

2008 ◽  
Vol 112 (37) ◽  
pp. 11819-11826 ◽  
Author(s):  
Pawel Szarek ◽  
Edyta Dyguda-Kazimierowicz ◽  
Akitomo Tachibana ◽  
W. Andrzej Sokalski
Keyword(s):  
Protein Kinase ◽  
Transition State ◽  
Intermolecular Interactions ◽  
Active Site ◽  
Transfer Reaction ◽  
Physical Nature ◽  
Phosphoryl Transfer ◽  
Dependent Protein Kinase ◽  
Transition State Stabilization ◽  
Dependent Protein

scholarly journals Fragment molecular orbital study of the cAMP-dependent protein kinase catalyzed phosphoryl transfer: a comparison with the differential transition state stabilization method

2016 ◽  
Vol 18 (22) ◽  
pp. 15153-15161 ◽  
Author(s):  
H. Öberg ◽  
T. Brinck
Keyword(s):  
Protein Kinase ◽  
Transition State ◽  
Molecular Orbital ◽  
Orbital Method ◽  
Phosphoryl Transfer ◽  
Dependent Protein Kinase ◽  
Fragment Molecular Orbital ◽  
Camp Dependent Protein Kinase ◽  
Transition State Stabilization ◽  
Dependent Protein

The importance of key residues to the activity of the cAMP-dependent protein kinase catalyzed phosphoryl transfer and to the stabilization of the transition state of the reaction has been investigated by means of the fragment molecular orbital method.

scholarly journals Insights into the phosphoryl transfer catalyzed by cAMP-dependent protein kinase

2014 ◽  
Vol 70 (a1) ◽  
pp. C449-C449
Author(s):  
Oksana Gerlits ◽  
Amit Das ◽  
Jianhui Tian ◽  
Malik Keshwani ◽  
Susan Taylor ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Active Site ◽  
Phosphate Group ◽  
Nucleoside Triphosphate ◽  
Phosphoryl Transfer ◽  
Hydrogen Atoms ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein

Protein kinases are involved in a number of cell signaling pathways. They catalyze phosphorylation of proteins and regulate the majority of cellular processes (such as growth, differentiation, lipid metabolism, regulation of sugar, nucleic acid synthesis, etc.). Chemically, protein kinases covalently transfer the gamma-phosphate group of a nucleoside triphosphate (e.g. ATP) to a hydroxyl group of a Ser, Thr or Tyr residue of substrate protein or peptide. The reaction involves moving hydrogen atoms between the enzyme, substrate and nucleoside. The unanswered question is whether the proton transfer from the Ser residue happens before the phosphoryl transfer using the general acid-base catalyst, Asp166, or after the reaction went through the transition state by directly protonating the phosphate group. To address this key question about the phosphoryl transfer, we determined a number of X-ray structures of ternary complexes of catalytic subunit of cAMP-dependent protein kinase (PKAc) with various substrates, nucleotides and cofactors. Importantly, we were able to trap and mimic the initial (Michaelis complex) and final (product complex) stages of the reaction. The results demonstrate that Mg2+, Ca2+, Sr2+, and Ba2+ metal ions bind to the active site and facilitate the reaction to produce ADP and a phosphorylated peptide. The study also revealed that metal-free PKAc can facilitate the phosphoryl transfer reaction; a result that was confirmed with single turnover enzyme kinetics measurements. Comparison of the product and the pseudo-Michaelis complex structures, in conjunction with molecular dynamics simulations, reveals conformational, coordination, and hydrogen bonding changes that help further our understanding of the mechanism, roles of metals, and active site residues involved in PKAc activity.

Substrate-mediated channeling of a chemical reagent to the active site of cAMP-dependent protein kinase

FEBS Letters ◽  
1981 ◽  
Vol 130 (1) ◽  
pp. 127-132 ◽  
Author(s):  
Juan S. Jiménez ◽  
Abraham Kupfer ◽  
Philip Gottlieb ◽  
Shmuel Shaltiel
Keyword(s):  
Protein Kinase ◽  
Active Site ◽  
Chemical Reagent ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein
Sign in / Sign up

Export Citation Format

Share Document