Interactions of calmodulin with death-associated protein kinase peptides: experimental and modeling studies

Journal of Biomolecular Structure & Dynamics
Krzysztof Kuczera, Petri Kursula

Abstract

We have studied the interactions between calmodulin (CaM) and three target peptides from the death-associated protein kinase (DAPK) protein family using both experimental and modeling methods, aimed at determining the details of the underlying biological regulation mechanisms. Experimentally, calorimetric binding free energies were determined for the complexes of CaM with peptides representing the DAPK2 wild-type and S308D mutant, as well as DAPK1. The observed affinity of CaM was very similar for all three studied peptides. The DAPK2 and DAPK1 peptides differ significantly in sequence and total charge, while the DAPK2 S308D mutant is designed to model the effects of DAPK2 Ser308 phosphorylation. The crystal structure of the CaM-DAPK2 S308D mutant peptide is also reported. The structures of CaM-DAPK peptide complexes present a mode of CaM-kinase interaction, in which bulky hydrophobic residues at positions 10 and 14 are both bound to the same hydrophobic cleft. To explain the microscopic effects underlying these interactions, we performed free energy calculations based on the approximate MM-PBSA approach. For these highly charged systems, standard MM-PBSA calculations did not yield satisfactory results. We proposed a rational m...Continue Reading

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Citations

Jan 28, 2014·Chemico-biological Interactions·Grace ChoongDouglas M Templeton
May 27, 2014·Journal of Molecular Biology·Alvaro VillarroelPilar Areso
Aug 28, 2015·Journal of Molecular Graphics & Modelling·Ahmad M AlmudallalJohn M Stewart
Apr 9, 2014·Journal of Biomolecular Structure & Dynamics·Mutangana Dieudonné, K V Ramesh
Jul 3, 2013·Journal of Biomolecular Structure & Dynamics·Mahesh Chandra PatraSurya Narayan Rath
Jan 15, 2014·Acta Crystallographica. Section D, Biological Crystallography·Petri Kursula

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Methods Mentioned

BETA
NMR

Software Mentioned

smMLCK
CHARMM
PBSA
Arp
Warp
MOLREP
skMLCK
REFMAC5
SOLVATE
Microcal Origin

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