Protein kinase biochemistry and drug discovery

PA Schwartz, BW Murray - Bioorganic chemistry, 2011 - Elsevier
Protein kinases are fascinating biological catalysts with a rapidly expanding knowledge
base, a growing appreciation in cell regulatory control, and an ascendant role in successful …

Magnesium increases insulin-dependent glucose uptake in adipocytes

LJ Oost, S Kurstjens, C Ma, JGJ Hoenderop… - Frontiers in …, 2022 - frontiersin.org
Background Type 2 diabetes (T2D) is characterized by a decreased insulin sensitivity.
Magnesium (Mg2+) deficiency is common in people with T2D. However, the molecular …

Phosphorylation reaction in cAPK protein kinase-free energy quantum mechanical/molecular mechanics simulations

M Valiev, J Yang, JA Adams, SS Taylor… - The Journal of …, 2007 - ACS Publications
We present results of a theoretical analysis of the phosphorylation reaction in cAMP-
dependent protein kinase using a combined quantum mechanical and molecular mechanics …

A conserved non-canonical motif in the pseudoactive site of the ROP5 pseudokinase domain mediates its effect on Toxoplasma virulence

ML Reese, JC Boothroyd - Journal of Biological Chemistry, 2011 - ASBMB
The ROP5 family is a closely related set of polymorphic pseudokinases that are critical to the
ability of Toxoplasma to cause disease. Polymorphisms in ROP5 also make it a major …

A Transition Path Ensemble Study Reveals a Linchpin Role for Mg2+ during Rate-Limiting ADP Release from Protein Kinase A

IV Khavrutskii, B Grant, SS Taylor, JA McCammon - Biochemistry, 2009 - ACS Publications
Protein kinases are key regulators of diverse signaling networks critical for growth and
development. Protein kinase A (PKA) is an important kinase prototype that phosphorylates …

Computational study of the phosphoryl transfer catalyzed by a cyclin‐dependent kinase

M De Vivo, A Cavalli, P Carloni… - Chemistry–A European …, 2007 - Wiley Online Library
A cyclin‐dependent kinase, Cdk2, catalyzes the transfer of the γ‐phosphate from ATP to a
threonine or serine residue of its polypeptide substrates. Here, we investigate aspects of the …

Insights into the phosphoryl transfer mechanism of cyclin-dependent protein kinases from ab initio QM/MM free-energy studies

GK Smith, Z Ke, H Guo, AC Hengge - The journal of physical …, 2011 - ACS Publications
Phosphorylation reactions catalyzed by kinases and phosphatases play an indispensible
role in cellular signaling, and their malfunctioning is implicated in many diseases. A better …

Role of Mg2+ ions in protein kinase phosphorylation: insights from molecular dynamics simulations of ATP-kinase complexes

L Yu, L Xu, M Xu, B Wan, L Yu, Q Huang - Molecular Simulation, 2011 - Taylor & Francis
Phosphorylation of protein kinases (PKs) plays a central role in the signal transduction of
cells by transferring a phosphate group from adenosine triphosphate (ATP) to the side …

Statistics of cellular signal transduction as a race to the nucleus by multiple random walkers in compartment/phosphorylation space

T Lu, T Shen, C Zong, J Hasty… - Proceedings of the …, 2006 - National Acad Sciences
Cellular signal transduction often involves a reaction network of phosphorylation and
transport events arranged with a ladder topology. If we keep track of the location of the …

Physical nature of intermolecular interactions within cAMP-dependent protein kinase active site: differential transition state stabilization in phosphoryl transfer reaction

P Szarek, E Dyguda-Kazimierowicz… - The journal of …, 2008 - ACS Publications
The origin of enzyme catalytic activity may be effectively explored within the nonempirical
theory of intermolecular interactions. The knowledge of electrostatic, exchange …