Event Information
Fitness through Simplicity: Dominance of the HAD Phosphotransferase Family
- Abstract:
The evolution of new catalytic activities and specificities within an enzyme superfamily requires the exploration of sequence space for adaptation to a new substrate with retention of those elements required to stabilize key intermediates/transition states. Phylogenetic analysis, mechanistic information, and structure determination is used to reveal novel ways in which the catalytic scaffold of a mechanistically diverse superfamily, the haloalkanoic acid dehalogenase enzyme superfamily (HADSF), is tailored to new biochemical functions. Steps (and mis-steps) in the understanding of substrate specificities in capless members of the superfamily are highlighted. We propose that core residues in the large enzyme family, form a “mold” in which the trigonal bipyramidal transition-states (TBPST) formed during phosphoryl transfer are stabilized by electrostatic forces. As a test for the operation of the trigonal bipyramidal phosphorane mold, X-ray crystal structure determination has been performed on a phosphatase complex that contains a tungstate ligand that is stabilized in an otherwise high-energy coordination state. The complex is compared to that of vanadate, as an example of a ligand that can more easily expand coordination geometry. A composite TBPST derived from the analysis of 12 liganded HADSF structures, reveals absolutely conserved elements which serve to stabilize the axial and equatorial atoms of the phosphoryl group-suprisingly many originate from the enzyme main chain. All work was performed in collaboration with Debra-Dunaway Mariano, University of New Mexico and supported by NIH GM061099.
Hosts: Dewey McCafferty and Matt Bentley
Departmental Seminar