High resolution crystal structure of the Phe223Leu mutant of methylenetetrahydrofolate reductase from E. coli

CHED 851

Melissa K. Thorstad, mkt807@truman.edu, Department of Chemistry, Truman State University, 100 E. Normal, Kirksville, MO 63501, Elizabeth E. Trimmer, trimmere@grinnell.edu, Department of Chemistry, Grinnell College, 1116 8th Ave., Grinnell, IA 50112-1690, and John J. Tanner, tannerjj@missouri.edu, Department of Chemistry, University of Missouri-Columbia, 125 Chemistry Building, 601 S. College Ave., Columbia, MO 65211.
The flavoprotein methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of methylenetetrahydrofolate to methyltetrahydrofolate using NADH as the hydride donor and FAD as an intermediate hydride acceptor/donor. The action of MTHFR influences folate levels, which in turn, affects plasma homocysteine levels. Elevated plasma homocysteine levels in humans are associated with an increased risk of cardiovascular disease and neural tube defects. As previous research has indicated a unique mode of NADH binding involving stacking interaction with Phe223, this work is aimed at determining the structural consequences of mutating Phe223 to Leu. The Phe223Leu mutant has been crystallized and the structure determined to 1.75 Å resolution using data collected at the Advance Light Source. Current work is focused on determining the structure of reduced Phe223Leu complexed with NADH.
 

Undergraduate Research Poster Session: Biochemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster

Division of Chemical Education

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008