Karen Allen Leads the Bridge Project: Functional Assignment in HAD Superfamily Phsphotransferases

Professor Karen Allen is leading the HAD Bridge Project of the NIH U54 award to the University of Illinois entitled “Collaborative Center for an Enzyme Function Initiative,” ($25 million over 4 years, John Gerlt, PI).  Known as “GLUE Grants,” these prestigious awards provide resources to currently funded scientists to form research teams to tackle complex biomedical problems that are beyond the means of any one research group. This consortium will facilitate the discovery of in vitro enzymatic and in vivo metabolic/physiological functions of unknown enzymes discovered in genome projects. The consortium is organized around five Bridging Projects and seven Cores.  Professor Allen and her collaborator, Professor Debra Dunaway-Mariano, University of New Mexico, were invited to lead the HAD Bridge Project based on their 15 years of investigations on the chemical and catalytic mechanisms of the phosphotransferases in the haloalkanoic acid dehalogenase (HAD) superfamily of proteins (“Mechanism and Function in HAD Phosphotransferases,” NIH R01 GM061099.  Their work has successfully uncovered and confirmed the structural determinants of substrate specificity in all three subfamilies of the superfamily and are using this knowledge to predict the substrates for enzymes of unknown function, identifying the associated metabolic pathways of at least six members from various bacterial species. The HAD efforts will be greatly extended, enhanced, and enabled by the other Cores and Bridging Projects of the consortium, including the Protein Core, the EN and AH Bridges, Sequence/Genome Analysis Core, Microbiology Core, Computation Core, and the Structure Core. In turn, the HAD Bridge Project, will afford comprehensive kinetic and mechanistic expertise to provide test cases for and utilize the facilities and expertise of the Cores.