Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98878
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity
Author: Moore, C.
Da Mota, S.
Mikolajek, H.
Proud, C.
Citation: Molecular and Cellular Biology, 2014; 34(12):2294-2307
Publisher: American Society for Microbiology
Issue Date: 2014
ISSN: 0270-7306
1098-5549
Abstract: Eukaryotic elongation factor 2 kinase (eEF2K) is the best-characterized member of the α-kinase family. Within this group, only eEF2K and myosin heavy chain kinases (MHCKs) have known substrates. Here we have studied the roles of specific residues, selected on the basis of structural data for MHCK A and TRPM7, in the function of eEF2K. Our data provide the first information regarding the basis of the substrate specificity of α-kinases, in particular the roles of residues in the so-called N/D loop, which appears to occupy a position in the structure of α-kinases similar to that of the activation loop in other kinases. Several mutations in the EEF2K gene occur in tumors, one of which (Arg303Cys) is at a highly conserved residue in the N/D loop. This mutation greatly enhances eEF2K activity and may be cytoprotective. Our data support the concept that the major autophosphorylation site (Thr348 in eEF2K) docks into a binding pocket to help create the kinase-competent conformation. This is similar to the situation for MHCK A and is consistent with this being a common feature of α-kinases.
Keywords: Humans; Neoplasms; Amino acids; Phosphothreonine; Protozoan proteins; Binding sites; Amino acid sequence; Catalytic domain; Conserved sequence; Protein structure, secondary; Structural homology, protein; Protein binding; Structure-activity relationship; Substrate specificity; Phosphorylation; Mutation; Models, molecular; Molecular sequence data; Calcium-calmodulin-dependent protein kinases; Elongation factor 2 kinase; HEK293 cells
Rights: © 2014 American Society for Microbiology. All Rights Reserved.
RMID: 0030035733
DOI: 10.1128/MCB.00388-14
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.