Research uncovers structural basis for multifunctionality of aminoacyl tRNA synthetases

Dec 14 2009

Research published in the December 13, 2009 edition of Nature Structural Biology uncovers the structural basis for the multifunctionality of aminoacyl tRNA synthetases. Aminoacyl tRNA synthetases are universal and essential enzymes of protein synthesis machinery found in all organisms. However, human synthetases and naturally occurring variants of these enzymes have additional activities that are vital to normal functioning of the complex human system biology, yet remain distinct from the basic protein synthesis activities. aTyr Pharma's proprietary product generating engine is developing new biotherapeutics based on the additional functions of tRNA synthetases and naturally occurring variants that are involved in pathways relevant to treatment of inflammatory diseases, cancer, metabolic disorders and neurological disorders.

Professor Xiang-Lei Yang of The Scripps Research Institute (TSRI), a scientific co-founder of aTyr Pharma, led the team that demonstrated how the structural mechanism of one form of tryptophanyl tRNA synthetase can inhibit the formation of new blood vessels. According to Paul Schimmel, Professor at TSRI, co-founder of aTyr Pharma and co-author on the paper, "Many groups have conducted research on the structural basis of the protein synthesis activities of tRNA synthetases, but this work published in Nature Structural Biology is among the first to show how one, single protein can have completely different activities and functions in humans, depending on where the activity takes place. It is fascinating to see how a structural feature required for a protein synthesis activity inside the cell is co-opted to disrupt a critical binding activity outside the cell."

According to Jeff Watkins, CEO of aTyr Pharma, "In the past few years, the laboratories of Professors Yang and Schimmel have established a whole new area of biological research: novel functions of naturally occurring proteins resected from ancient proteins such as tRNA synthetases. aTyr Pharma's portfolio capitalizes on this new area of biology by using these naturally occurring proteins - and their previously unknown roles - to treat a wide variety of diseases. Uncovering the structural basis for the binding of resectins to natural ligands on human cells is an important step in determining how resectins can be used therapeutically, and we are happy that scientists from aTyr Pharma could contribute to this publication." Scientists at aTyr Pharma contributing to this paper include Rajesh Belani, Chulho Park, Eva Armour, Min-Ha Do and Leslie Nangle.