Drug Designing: Open Access
Open Access

Ser-51 phosphorylation of translation initiation factor 2a: Specificity determinants with respect to domain context

International Conference and Exhibition on Computer Aided Drug Design & QSAR

October 29-31, 2012 DoubleTree by Hilton Chicago-North Shore, USA

Madhusudan Dey and Brian Rick Mann

Accepted Abstracts: Drug Design

Abstract :

The Ser-51 phosphorylation of eukaryotic translation initiation factor 2a (eIF2a) is a fundamental regulatory mechanism of both general and gene-specific protein synthesis under conditions of various cellular stresses. Five eIF2a kinases PKR, PERK, PKZ, GCN2 and HRI specifically phosphorylate the Ser-51 residue of eIF2a. Both kinase and substrate act in a coordinated manner to maintain the specificity of Ser-51 phosphorylation. Recently, we reported that Ser-51 phosphorylation requires an induced conformational change of the local phosphorylation site sequences, collectively called the Ser-51 loop(Dey et al., 2011). To gain deeper mechanistic insights into Ser-51 phosphorylation we changed the position of the phospho-acceptor site in the target loop, and also substituted upstream and downstream neighboring residues of the target phospho-acceptor site by alanine individually and in combination. Here we show that there are two potential phospho-acceptor locations in the target loop. Importantly, phosphorylation of only one position is critical for the physiological adaptation to cellular stresses. Further, our results show that although specificity determinants for phosphorylation reside in the Ser-51 loop, the domain context is critical for the Ser-51 phosphorylation.

Biography :

Madhusudan Dey has completed his Ph.D at the age of 29 years from Jawaharlal Nehru University, New Delhi, India and postdoctoral studies from National Institutes of Health. He is an Assistant Professor in the Department of Biology at University of Wisconsin-Milwaukee. He has published more than 10 papers in reputed journals.