Boston University Department of Biology

Faculty Profiles

Current Research

Virtually all organisms contain the glycolytic enzyme fructose bisphosphate aldolase. Vertebrates have three distinguishable isoforms of the enzyme; aldolase A, B, and C. Each of these isozymes has different tissue distribution and catalytic properties appropriately for their roles in sugar metabolism. The aldolases have also been implicated in a number of moonlighting functions involved in cell motility, infection, insulin signaling, and endocytosis. It is the goal of the laboratory to understand the biochemical, evolutionary, and developmental mechanisms responsible for the distinguishing features of the various aldolases.

Structure and function of aldolases — The structural and functional details of this ancient and essential glycolytic enzyme are being investigated by structural analysis via x-ray crystallography and electron microscopy of the structures of the different isozymes complexed with substrate or inhibitor.

Characterization of the genetic defects in hereditary fructose intolerance (HFI) — Mutations in the aldolase B gene manifest themselves in HFI, a genetic disorder that can cause liver disease, coma, and death. It is especially problematic for newborn infants at the time they are weaned to fructose-containing foods. A mouse knock-out model is being used to study the disease and mutations from HFI patients of different ethnic groups are being determined.

Evolution of the aldolases — Current projects include the characterization of moonlighting functions that have evolved by oblating these functions with RNAi and mutant forms of the enzyme in tissue culture cells.

Courses Taught

• BI 421 Biochemistry I
• BI 527 Biochemistry Laboratory
• MB 722 Advanced Biochemistry

Selected Publications

• Pezza JA, Stopa JD, Brunyak EM, Allen KN, Tolan DR (2007). Thermodynamic analysis shows conformational coupling and dynamics confer substrate specificity in fructose-1,6-bisphosphate aldolase. Biochemistry 46, 13010-13018.
• Funari VA, Crandall JE, Tolan DR (2007). Fructose metabolism in the cerebellum. Cerebellum 6, 130-140.
• Choi KH, Lai V, Foster CE, Morris AJ, Tolan DR, Allen KN. (2006). New superfamily members identified for Schiff-base enzymes based on verification of catalytically essential residues. Biochemistry 45, 8546-8555.
• Malay AD, Allen KN, Tolan DR (2005). Structure of the thermolabile mutant Aldolase B, A149P: Molecular basis of hereditary fructose intolerance. Journal of Molecular Biology 347, 135-144.
• Funari VA, Herrera VLM, Freeman D, Tolan DR (2005). Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum. Molecular Brain Research 142, 115-122.
• Arakaki TL, Pezza JA, Cronin MA, Hopkins CE, Zimmer DB, Tolan DR, Allen KN (2004). Structure of human brain fructose 1,6-(bis)phosphate aldolase: linking isozyme structure with function. Protein Science 13, 3077-3084.
• Choi KH, Tolan DR (2004). Presteady-state kinetic evidence for a ring-opening activity in fructose-1,6-(bis)phosphate aldolase. Journal of the American Chemical Society 126, 3402-3403.
• Pezza JA, Choi KH, Berardini TZ, Beernink PT, Allen KN, Tolan DR. (2003). Spatial clustering of isozyme-specific residues reveals unlikely determinants of isozyme specificity in fructose-1,6-bisphosphate aldolase. Journal of Biological Chemistry 278, 17307-17313.