February 27, 2007
In 1981, NIDCR scientist Dr. Myung Hee Park noticed formation of a novel polyamine-derived amino acid in one specific protein from human peripheral lymphocytes, a type of immune cell. After much investigation, Park and her colleagues identified it as a unique amino acid called hypusine. Hypusine is produced by all eukaryotes but intriguingly occurs only in one protein known as eukaryotic translation initiation factor 5A (eIF5A). What has fascinated Park and other biochemists is that, despite billions of years of human evolution and all of the tens of thousands of proteins produced in the body, two enzymes still dutifully modify exclusively the eIF5A precursor to activate this protein. As they have noted, eIF5A and its hypusine modification are essential for proliferation of mammalian cells. The first enzyme modifies a lysine residue to form deoxyhypusine in the intermediate eIF5A protein. Then a second enzyme called deoxyhypusine hydroxylase (DOHH) adds a hydroxyl group to the deoxyhypusine residue to form hypusine. Now, Park and her NIDCR colleagues have published online in the Journal of Biological Chemistry the structural basis of the specificity of the DOHH-eIF5A interaction. They defined the specific amino acid residues of DOHH that are critical for binding the deoxyhypusine-containing eIF5A and suggest a structural model for this interaction. Still to be determined is the precise function of eIF5A and its mode of action in eukaryotic translation and cell proliferation.