Exactly what is going wrong is still unclear, adds Gerald Hart, Ph.D., professor and director of biological chemistry. He's been studying O-GlcNAc since his lab discovered it attached to proteins inside cells 20 years ago. They now know which enzymes put the sugar onto proteins and which enzymes take it off -- and knocking out or blocking these enzymes allowed the researchers to control whether proteins were sugar-laden or sugar-free.
"Normally, the enzyme that adds the sugar to proteins is enriched at the hub of activity during cell division," notes Slawson. "When we knock it out or block it with a chemical, the cell cycle lengthens and cell division doesn't happen properly. Clearly the enzyme is there for a reason."
But understanding what the sugar itself is doing and how its presence on or absence from proteins affects the cell depends solely on what protein it's being attached to or removed from.
"Whether it's turning something on or off depends on the protein to which the sugar is attached," says Hart. "It's harder than having discovered an enzyme that does just one thing. To figure out the sugar's effect, we have to look at what it's modifying, and the extent and the location of the modification."
The sugar seems to modify as many proteins as the ubiquitous phosphate groups widely recognized as protein controllers, and it frequently seems to compete with phosphate groups for the same spots on proteins. Hart suggests that a particular balance between O-GlcNAc and phosphates on proteins may help fine-tune their activities.
The researchers' next steps are to examine select prote
Source:Johns Hopkins Medical Institutions